Treatment of type 2 diabetes: drugs that reduce the risk of complications
How to treat type 2 diabetes?
Type 2 diabetes is a complicated disease in which several factors play a role and contribute differently to the development of diabetes. The body develops a disturbance in the circulation of blood sugar which eventually leads to a rise in blood sugar levels. Two important factors for type 2 diabetes are that the body produces too low levels of the hormone insulin or the hormone has a reduced effect in the body. When the body develops a reduced sensitivity to the hormone insulin, you suffer from a condition called insulin resistance.
Recently, researchers have discovered that type 2 diabetes is a condition where several different metabolic disorders occur in the body, even in people who do not have insulin resistance (which is a very small percentage), people with type 2 diabetes are more likely to suffer serious complications. and premature death compared to people without diabetes.
Cardiovascular diseases are the most common and feared complications of type 2 diabetes and are usually divided into two main groups, macrovascular and microvascular complications. These expressions describe in which part of the vascular tree the disease occurs. Microvascular complications affect the smallest blood vessels called capillaries, arterioles and venules. These blood vessels are very small and have a diameter of 100 mm (micrometer).
The National Diabetes Register (NDR) shows that of all people with type 2 diabetes in Sweden, 20% have suffered complications in the blood vessels that supply the heart muscle (coronary heart disease), 8% have stroke and 8% suffer heart failure. These complications are 2-4 times more common compared to peers without diabetes.
NDR has also studied the incidence of microvascular complications, where it has been observed that of all people with type 2 diabetes in Sweden have 30% changes in the small blood vessels that supply the retina of the eyes and the smallest filtration system of the kidneys. The risk of diabetes-related complications is greater in individuals who have had diabetes for many years (long diabetes duration). In people with type 2 diabetes who have had the disease for more than 5 years, about half has some form of vascular disease.
Complications arising from type 2 diabetes can be prevented or delayed by intensive treatment of several known risk factors, such as high blood sugar (hyperglycaemia), high blood pressure (hypertension) and elevated blood lipidemia (dyslipidemia). In addition to these traditional and medically modifiable risk factors, there is also convincing evidence that smoking, low physical activity and poor diet contribute significantly to the development of cardiovascular diseases and premature death in people with type 2 diabetes.
In this article, we will review treatment recommendations and goals for various drugs that act against high blood sugar (hyperglycemia) in type 2 diabetes. International consensus on treatment targets for blood sugar in individuals with type 2 diabetes is a long-term blood sugar (HbA1c) ≤ 6.5%.
The treating physician should consider several clinical factors before determining the treatment goals together with the patient. People with diabetes who have not had their disease for years, have no previous cardiovascular disease, have a low risk of severe blood sugar falls (hypoglycaemia) or other co-morbidity are usually treated with intensive blood sugar lowering therapy. Intensive blood glucose lowering treatment is an expression that is often used in discutions.
These factors usually also mean that other risk factors for cardiovascular diseases are not treated particularly intensively, such as high blood pressure (hypertension) high blood lipidemia (hyperlipidemia).
How a doctor treats blood sugar is also based on various factors, those with diabetes who have had their illness for a very long time, have a history of high blood glucose levels, other serious co-morbidity or high risk of severe blood sugar falls (hypoglycaemia). that the treated doctor accepts higher levels of long-term blood sugar (HbA1c). The reason for this is that the blood glucose levels rise gradually the longer the person has lived with the disease, regardless of ongoing treatment, some treatments however have a severe slowing effect against this development, such as insulin and gastric bypass surgery.
The body adapts to the rising levels of blood sugar, which means that a relatively large fall in blood sugar (hypoglycaemia) causes significantly greater damage to the body than the complications of atherosclerosis. It is mainly brain cells that suffer most from sudden blood sugar falls, but some studies also suggest that hypoglycaemia can cause instability in the bloodstream plaques found in our blood vessels.
Lower your blood sugar
The aim of treating type 2 diabetes is to achieve symptom freedom, maintain a high quality of life and prevent future diabetic complications such as cardiovascular diseases (micro- and macrovascular complications) while maintaining a high quality of life.
People with type 2 diabetes not only suffer from late complications such as cardiovascular diseases but also acute complications, including ketoacidosis, which may sometimes be due to a complication of metformin therapy or increased blood sugar levels due to poor treatment. Another common condition is severe blood sugar fall (hypoglycaemic episode) and hyperglycaemic hyperosmolar syndrome.
Another goal for people with diabetes is to be free from diabetes symptoms, such as increased urine output (polyuria), increased thirst, fatigue and visual impairment (accomodation disorders), which speak for elevated blood sugar levels. This affects the quality of life and is an important goal in the treatment of diabetes.
Patient education is a central part of diabetes care and greater emphasis should be placed on providing the patient with knowledge and security, especially in complex treatment situations. Patient education should strive to provide all patients with the instruments to take control of their life situation and illness. Change in lifestyle habits is an important cornerstone in the treatment of diabetes.
- A long-term goal in diabetes is to reduce the appearance of visual impairment, kidney damage, foot ulcers, amputations, cardiovascular disease and other diabetic complications.
- Good control of blood sugar levels can slow the progression of organ damage in the eyes, kidneys and feet. This can lead to severe organ damage that ultimately affects the health and life of the individual.
Goals for blood glucose control should always be individualized from the perspective of the patient. A simple rule is that very good blood sugar control is preferable if the person is not seriously ill for various reasons. During the honeymoon phase of type 1 diabetes and in case of newly discovered type 2 diabetes, blood sugar levels should be treated to normalize. Women who develop gestational diabetes should be treated to normal blood sugar levels in order to increase the chances of a favorable outcome.
During adolescence, it is more difficult to control blood sugar levels partly because of the hormone GH (Growth hormone) which potentiates insulin resistance. Perfect glucose control in such situations can be difficult to achieve and strict goals can lead to failure and disappointment, this can have negative consequences for blood sugar control in the future for people with diabetes.
Check blood sugar regularly
Patients with type 2 diabetes are recommended to measure blood glucose levels (HbA1c) two to four times a year, and patients who have ongoing drug therapy should also measure their blood sugar levels more frequently. The number of annual checks is determined individually, but usually 4 checks are recommended annually for all individuals with type 2 diabetes.
For people with type 2 diabetes, the treating physician must take into account age, life expectancy and other co-morbidity, such as cardiovascular disease or other diabetic complications. Patients and doctors should strive for a normalized blood sugar value.
Other risk factors for complications
Individuals with diabetes should focus on influencing other risk factors for cardiovascular disease, such as overweight, obesity, high blood pressure, cholesterol and smoking, as well as an individual risk assessment for cardiovascular disease. Multifactorial risk intervention is common for people with diabetes, which involves treating several risk factors for cardiovascular disease at the same time. A large proportion of all patients with type 2 diabetes have several other risk factors for cardiovascular diseases, therefore it is not uncommon for these patients to receive several different drugs that protect the heart and blood vessels.
Drug Studies in Diabetes and Cardiac Vessels
In 2008, several research studies were published that investigated the efficacy of various drugs against elevated blood sugar levels in individuals with type 2 diabetes, these studies have contributed significantly to the current health care guidelines for type 2 diabetes.
However, the results of these drug trials were difficult to interpret and partly contradictory, one of these studies called ACCORD was discontinued prematurely as individuals treated with intensive blood glucose lowering therapy were at greater risk of cardiovascular disease.1
Two talked about drug trials in diabetes called VADT and ADVANCE showed that the risk of cardiovascular disease was not less in those with intensive blood sugar treatment. This means that these studies do not support that lower blood sugar levels than today’s recommended levels would be better for the individual with diabetes 2.3
Drug studies that studied the effectiveness of intensive blood glucose lowering therapy have different definitions of intensive therapy, the majority of studies consider long-term blood sugar (HbA1c) in subjects with type 2 diabetes that are approximately ≤ 42 mmol/mol or ≤ 48 mmol/mol to have intensive treatment. In diabetes care, there are several recommendations for different situations where there is no evidence, several of our national treatment recommendations are determined by expert groups in diabetes.
Intensive glucose-lowering treatment
December 2008, research findings were published from the famous study Veterans Affairs Diabetes Test (VADT), a long-term study investigating the effect of intensive blood sugar control on American war veterans with type 2 diabetes.
The results show that intensive blood glucose lowering therapy contributes to an increased risk of cardiovascular disease and early death in individuals with type 2 diabetes, the findings from VADT are consistent with the results of two other comprehensive drug trials ACCORD and ADVANCE.
However, the Advance study showed that intensive blood glucose lowering therapy reduced the development and worsening of microvascular complications, but without any effect on cardiovascular events. ACCORD was stopped early due to an increased risk of death in patients who underwent intensive blood glucose lowering.
Some of the authors of the studies believe that the results are partly due to high co-morbidity and long diabetes duration among many of the study participants involved in the studies. In VADT, the mean age was 60 years among the study participants, most of them had high blood pressure, elevated blood lipids and sharply elevated blood sugar levels. The authors believe that the long diabetes duration and their previous blood glucose levels were probably the reason why intensive blood glucose lowering treatment increased the risk of cardiovascular disease.
In addition, it is known from previous diabetes studies that the effect of low blood glucose lowering therapy is only seen many years after the patient has decreased blood sugar levels.
Recommended blood sugar levels
|Target values for long-term blood sugar (haemoglobin A1c, HbA1c)|
|In patients with type 2 diabetes who strive for symptom freedom from high blood sugar than prevention of late complications, the target of HbA1c is < 8-9%.|
|Target values for blood sugar|
|Not under||Not above|
|Blood sugar before meal, mmol/L||4,5||8|
|Blood sugar 2 hours after meal, mmol/L||4,5||10|
These limits of blood glucose levels should be sought by every person with type 2 diabetes, and the lower limit should not be perceived as a target value to strive for, but should not be undercut. In patients with type 2 diabetes who only want to achieve symptom freedom and not prevent complications, the upper limit of approximately 9 mmol/L and 12 mmol/L is recommended before and after meals. Target values for these patients only apply to the upper limits, because the primary aim is to avoid serious blood sugar falls at all costs.
Legacy effect in blood sugar lowering treatment
A known UK drug trial called the United Kingdom Prospective Diabetes Study (UKPDS) showed that individuals with type 2 diabetes treated with intensive blood glucose lowering therapy for a number of years had a lower risk of small vascular complications that lead to to organ failure, nerve damage and eye complications. However, this study did not observe any reduction for the dreaded complications, heart attack and stroke.
Earlier in this chapter, we discussed the study that first examined whether people with type 1 diabetes benefit from intensive treatment for high blood sugar, namely the DCCT study. In a follow-up study to DCCT named DCCT/EDIC, the study authors noted that intensive treatment for blood sugar also has a positive effect against complications such as acute myocardial infarction and stroke.
In drug trials that study the effectiveness of blood sugar lowering drugs, it is not uncommon for the effect to be seen several years after the person has lowered blood sugar levels. As with the DCCT study, a follow-up study was published ten years after the end of UKPDS, the study participants from the first drug trial had been examined and the study participants studied. Also in this follow-up study, people who were offered intensive blood glucose lowering treatment were at a lower risk of macrovascular complications, such as heart attack and stroke.
What is interesting about these two studies is that people who underwent intensive blood glucose lowering treatment had about the same blood sugar levels as the second treatment group only one year after the drug trial was completed, despite this, a clear effect was seen many years after study completed. This means that intensive blood glucose lowering treatment for just a few years has a signatory effect on cardiovascular complications, although blood sugar levels rise rapidly to their original levels when the study is terminated.
The researchers behind the studies believe that people with type 2 diabetes have a lower risk of macrovascular complications only after a few years. At the same time, these drug trials show that the positive effect of intensive treatment continues to protect the individual many are after the “protective effect” well enters, this phenomenon was renamed the “legacy effect”. 4
The results have led many drug trials to show blood glucose lowering effects but not a clear difference for other events such as death, acute heart attack or stroke.
Intensive treatment of blood sugar – good, but difficult
Intensive blood glucose control therapy had a major breakthrough in 1993 following a study called The Diabetes Control and Complications Trail (DCCT), which showed that long-term blood sugar reduction (HbA1c) could prevent vascular disease in individuals with type 1 diabetes, in this study It was noted that a percentage point decrease in long-term blood sugar (HbA1c) resulted in a 25% reduction in cardiovascular disease, these results were initially extrapolated to individuals with type 2 diabetes before more specific drug trials were conducted for type 2 diabetes.
|Various factors to consider when initiating insulin therapy in type 2 diabetes|
|Does the patient follow the recommendations regarding diet, exercise and drug therapy?|
Is there a reason why the individual with type 2 diabetes has insulin deficiency, should C-peptide be measured?
Are there any factors that suggest that the person actually has a variant of diabetes that is more similar to type 1 diabetes?
Other cause of insulin deficiency, such as pancreatic cancer or repeated pancreatic inflammation.
Are there other conditions that lead to impaired body function (insulin resistance)
– Elevated blood lipids that are untreated
– Other diseases in hormonal organs that can cause insulin resistance
– Medicines that cause diabetes symptoms for various reasons
Treatment objectives in type 2 diabetes
Today’s treatment goals are mainly based on clinical drug trials, epidemiological investigations, observational studies or by extrapolation of other studies involving different patient groups.
A well-known study called the United Kingdom Prospective Diabetes Study (UKPDS) showed that a decrease in long-term blood sugar (HbA1c) of 10 mmol/mol between 53 mmol/mol in the intensive treatment group and 63 mmol/mol in the control group resulted in approximately 25% reduction in small- vascular disease (microvascular) complications, kidney damage and vascular damage of the fundus), the onset of myocardial infarction decreased even by 16% .5.6
The unit of long-term blood sugar is indicated in the form of hemoglobin A1c, it is important to note that the method used to measure HbA1c in UKPDS does not correspond to our HbA1c values obtained by the Mono-S method in Swedish hospital laboratories. In the Swedish National Guidelines for Care and Treatment in Diabetes Mellitus, the target values for good blood glucose control have been determined to be 6.5% while individuals with HbA1c 7.5% have an unsatisfactory control.
According to the International Diabetes Federation (IDF) and many regions of the EU, individuals with HbA1c 48 mmol/mol are considered to be at a lower risk of developing cardiovascular disease.
Diagnostic limits according to WHO for type 2 diabetes are HbA1c ≥ 48 mmol/mol, people without diabetes have 42 mmol/mol. When sampling venous plasma glucose (blood sugar levels), type 2 diabetes is diagnosed at values, ≥ 7.0 mmol/L on fasting and at blood sugar levels above ≥ 11.1 mmol/L 2 hours after food are signs of poor blood sugar control. For blood samples taken at the bottom of the finger peaks, these world is approximately one unit larger.
|Treatment goals for blood sugar in individuals with type 2 diabetes|
|Organization||Long-term blood sugar |
– HbA1c (mmol/mol)
|fP-glukos (mmol/L) |
|Blood sugar after eating|
– Postprandiel P-glukos (mmol/L)
|American Diabetes Association (ADA)||< 53 mmol/mol|
|International Diabetes Federation (IDF)||≤ 48||≤ 6,0 mmol/L||≤ 7,5 mmol/L|
|American Association of Clinical Endocrinology (AA CE)||≤48||≤ 6,0||≤ 7,8|
|European Society for Cardiology (ESC) and European
Association for the Study of Diabetes (EASD)
|<48 – 53|
|National Institute for Health and Clinical Excellence (NICE), UK||≤48|
|Swedish Association for Diabetes||<42||< 6||< 8|
In clinical practice, different levels of HbA1c are usually sought depending on diabetes duration, life expectancy of the patient, absence of manifest cardiovascular disease, absence of other serious disease. Patients who have a short diabetes duration (5-10 years) and meet the other above criteria are expected to be between 42-52 mmol/mol in HbA1c.
For people with type 2 diabetes with a longer diabetes duration (10 years), other co-morbidity or difficulties in achieving lower blood sugar levels due to repeated blood sugar falls (hypoglycaemic episodes), blood glucose values are usually sought between 53-69 mmol/mol in HbA1c, the upper values usually. Most often it is allowed to people with biological age over 80 years, manifested by cardiovascular diseases and a pronounced risk of falling blood sugar.
This chapter deals with tablet treatment at type 2 diabetes but several individuals with type 2 diabetes also require insulin that addition to tablet therapy to control their blood sugar levels. Most people with newly onset type 2 diabetes begin treatment with a combination of diet, exercise and tablets. Over time, some people will have to lay to insulin or other injectable medication because their blood sugar levels is not well controlled. In some cases, insulin is recommended (or other injectable drugs) first, as initial treatment. Your caregiver will be talking to you about your options and goals, and collaborate with you to make a treatment plan.
Types of insulin
There are several types of insulin. These types is classified according to how quickly the insulin begins to function and how long it remains active:
- Insulin lispro (brand: Humalog)
- Insulin aspart (brand: Novolog)
- Insulin glulisin (brand: Apidra)
- Insulin NPH (brand: Humulin N)
- Insulin lispro protamin (mixed with fast acting insulin lispro [brand: Humalog Mix])
- Insulin glargin (brand: Lantus)
- Insulin detemir (brand: Levemir; intermediate to long-acting; could be needed twice daily)
- Insulin degludec (brand: Tansiba)
- Insulin glargin 300 units/ml (brand: Toujeo)
A form of inhaled insulin (brand: Aprezza) is available in the United States. Inhaled insulin has not been shown to lower A1C levels to the usual target level of less than 7 percent in most studies. Plus, a pulmonary function test is required before it is started and periodically during treatment. For these reasons, inhaled insulin has not been widely used.
Initial dose of insulin
When insulin is started for type 2 diabetes caregivers usually recommend “basal” insulin; this means taking medium acting and/or long-acting forms of insulin to keep blood sugar checked throughout the day. You will most likely need to take basal insulin once a day, either in the morning or before bedtime.
If you use a combination of treatments (ie an oral medicine plus insulin), it generally means that you can take a lower dose of insulin compared to people who only take insulin. Because insulin may cause weight gain in the long term, combination therapy may reduce the risk of weight gain. Your caregiver will cooperate with you to monitor your body’s response and adjust the dose over time.
Type 2 diabetes usually progresses over time, causing the body to produce less insulin. Some people need a more complex insulin therapy. In this situation, a dose is added before meal of fast-acting or short-acting insulin to the dose of basal insulin once a day. As a first step, meal insulin can be started as a single injection before the main meal of the day, but your caregiver may suggest another approach. The dose of short-acting or fast-acting insulin is adjusted immediately before a meal. The dose needed depends on many different factors, including your current blood sugar level, your diet’s carbohydrate content and your activity level.
People with type 2 diabetes are sometimes treated with “intensive” insulin regimens. Intensive insulin therapy requires several injections of insulin per day or use of an insulin pump. It requires also measurement of blood sugar levels several times a day, with adjustment of Insulin dosage before meals based on the size and carbohydrate content of the meal. This approach is more often used in people with type 1 diabetes.
Insulin can not be taken in tablet form. It is usually injected into the fat layer under the skin (called “subcutaneous” injection). You can inject insulin into different parts of the body. You will need to learn how to use an insulin-pen or, if you are using a needle and syringe, pick up and inject your insulin. You can also teach your partner or a family member how to a man gives insulin.
Pencils are especially useful to accurately inject very small doses of insulin and may be easier to use if you have vision problems. Pencils are more expensive than traditional syringes and needles. A number of different insulin pens are available. If your caregiver prescribes a pen for you, it will be supplied with special instructions for use.
Needle and syringe
Some people use a needle and syringe (instead of a pen) to give themselves insulin. This means to withdraw insulin from a vial by syringe and then inject it with a needle under the skin.
Before taking up insulin, it is important to know what dose and type of insulin is needed. If you use more than an insulin type, you must calculate the total dose needed (your healthcare provider will show you how to do this). Some people, including children and people with vision problems, may need help. Magnification and other aids are available. If you have difficulty producing your insulin, let your caregivers know, because there are ways to help in this.
Insulin is usually injected under the skin. It is important to use the correct injection angle as injection too deep may result the insulin gets into the muscle, where it is absorbed too quickly. On the other hand are injections that are too shallow more painful and are not well absorbed.
The best angle of insulin injection depends by body type, injection site and length of the needle used. Your caregiver can help you figure out what length needle to use and in what angle the insulin should be injected.
These are the basic steps of injection of insulin:
- Select the injection site. You do not need to clean your skin with alcohol unless your skin is dirty.
- Grasp a piece of skin fold and quickly insert the needle at an angle of 90° (or the angle you have discussed with your caregiver). Keep the skin clamped to avoid injecting insulin into the muscle.
- Inject the insulin. Hold the syringe and needle in place for 5 seconds for syringes and 10 seconds for insulin pens.
- Release the skin.
- Remove the needle from the skin.
If you see blood or clear fluid (insulin) at the injection site, press the area for a few seconds. Do not rub the skin, as this can lead to the insulin being absorbed too quickly. Each needle and syringe should be used once and then thrown away. The needles quickly become bad, which can increase the pain when injected. Needles and syringes should never be shared.
Factors affecting the effectiveness of insulin
Several factors may affect how injected insulin works.
Dose of injection
The injection dose affects the rate with which the body absorbs it. Larger doses of insulin can be absorbed more slowly than smaller doses.
The injection site
It is very important to rotate injection sites (i.e. avoid using the same site each time) to minimize tissue irritation or damage. When changing the racks, it is important to remember that insulin is absorbed at different rates in different parts of the body. Insulin is most quickly absorbed from the abdominal area, slowest from the leg and buttock, injecting insulin into the arm is slightly faster than the leg but still slower than the abdominal fat. This may vary depending on the amount of fat contained, areas with more fat under the skin absorb insulin slower.
It is reasonable to use the same area for insulin given at the same time of day. For example, abdominal injections are preferred, such as absorbed faster, before meals. Injection into the thigh or buttock can be best for the evening dose because the insulin is absorbed more slowly during the night.
Smoking and physical activity
All factors that change the blood flow through skin and fat will change insulin absorption. Smoking decreases blood flow, which in turn reduces insulin absorption. However, increasing activities that increase blood flow (such as exercise, sauna, hot baths and massage injection site) insulin absorption and may result in hypoglycaemia (low blood sugar). For these reasons, it is best to avoid injecting your insulin immediately after any of these activities. Your caregiver can also recommend that you take a lower dose of insulin before or after exercise.
The same dose of the same type of insulin may have different effects in different people with diabetes. Some attempts and errors are usually necessary to find the ideal dose of insulin and schedule for each person.
The insulin dose often needs to be adjusted during a person’s lifetime. Changes in weight, diet, state of health (including pregnancy), level of activity and occupation can affect the amount of insulin needed to control blood sugar levels. Your caregiver can teach you to adjust your own insulin dose as needed, but this depends on your specific situation. See also our patient training on how to write diabetes diary with information about insulin doses, sugar levels, meals, activities to determine how to adjust insulin.
Individuals who have just developed type 2 diabetes (newly onset) and who do not have severe renal impairment are usually offered treatment with a medicine called Metformin. This drug has probably been studied most extensively in the treatment of high blood sugar in individuals with type 2 diabetes.7.8
How does Metformin work
Metformin lowers blood sugar levels in several ways. Among other things, it reduces the formation of sugar in the liver (gluconeogenesis) while Metformin increases the absorption of sugar (glucose) in the skeletal muscles of the body. The treatment thus causes a decrease in blood sugar levels by reducing the excretion of sugar into the blood while simultaneously absorbing blood sugar from the blood into tissues that need glucose.
Metformin is considered to enhance the sensitivity to insulin in insulin sensitive tissues such as liver, skeletal muscle and adipose tissue. For this reason, it is usually said that Metformin reduces insulin resistance, remember that insulin resistance is a central factor in the development of type 2 diabetes.
In type 2 diabetes, there are several different treatment options that work by stimulating the release of the hormone insulin from the body’s only insulin-producing organ, namely pancreas (pancreas). Unlike other medicines, Metformin does not cause pancreatic insulin secretion and therefore cannot cause serious blood sugar drops (hypoglycaemic episodes).
Metformin has the following mechanisms of action
- Reduction of the liver’s production of sugar by inhibiting the formation and breakdown of sugar (gluconeogenesis and glycogenolysis)
- By increasing sensitivity to insulin, improving sugar absorption and utilization of sugar in the musculature
- Delay of sugar absorption from the gastrointestinal tract
Recent research also shows that Metformin has a beneficial effect on our bacterial flora in the gastrointestinal tract (microbiota), treatment with Metformin leads to the secretion of hormones (eg GLP-1) from the gastrointestinal tract, which have a positive effect on sugar metabolism.
Some studies show that Metformin stimulates the production of glycogen inside our cells by affecting a protein called glycogen synthetase. Another theory is that Metformin enhances the capacity of cells to transport sugar (GLUT receptors).
Side effects from Metformin
Metformin is generally well tolerated but usually causes gastrointestinal side effects (stomach pain, gases, nausea, constipation and sometimes diarrhoea). Metformin is likely to cause more side effects in the gastrointestinal tract than many other tablet treatments but is well tolerated if the dose of the medicine is gradually increased and taken with meals.
Metformin can affect the absorption of vitamin B12, as well as cause a decrease in two important substances called Cobalamin and Folate, when the body has too low levels of these substances it can lead to anemia. However, this condition is very rare.
Individuals with severe renal impairment should not start treatment with Metformin as the medicine is excreted by the kidneys. In severe renal impairment, various residues from the degradation of the drug (metabolites) may accumulate in the body. This can lead to an unusual but life-threatening metabolic complication called lactic acidosis.
The individuals with type 2 diabetes who are most at risk of lactic acidosis are individuals with diabetes and renal failure, elderly age, liver disease, dehydrated or excessive alcohol consumption.
However, recent research has shown that the risk of lactic acidosis in individuals with type 2 diabetes and impaired renal function is lower than previously known, but in everyday clinical practice the doctor still recommends other medicines if the patient suffers from renal impairment.
People who overdosed with Metformin may develop lactic acidosis, which is a life-threatening complication requiring immediate medical attention. Other symptoms of overdose may be severe drowsiness, severe nausea, vomiting, diarrhea, rapid breathing in combination with slow and irregular heart rhythm. People with type 2 diabetes overdosed with Metformin describe a very unpleasant general malaise.
Clinical effects of Metformin
In the large drug study called UKPDS noted that overweight individuals with newly discovered type 2 diabetes have a lower risk of several diabetes-related complications when using this drug.8 Metformin reduces long-term blood sugar (HbA1c) by approximately 1-1.5 percentage points, corresponding to 10 — 15 mmol/mol and are considered to be at least as effective or slightly better than the other tablet treatments in type 2 diabetes, and guaranteed to be more effective than the drug Akarbos or DPP4 inhibitors.9
Metformin treatment should always be combined with a proper diet and exercise regimen and also be combined with several other medicines for type 2 diabetes, including insulin. The beneficial effect of Metformin increases at higher doses, therefore daily doses of 1500 mg to 2500 mg per day should be sought, a daily dose of around 2000 mg is often counted as a reasonable maximum dose, but in some patients it may be appropriate to try a higher dose, though never higher than 3000 mg.7 However, even with small In the dosage of the drug, a favorable effect is observed.
Metformin can reduce cardiovascular diseases even at a low dose of 500 mg, which may motivate the patient to continue low-dose treatment, many patients experience gastrointestinal side effects from Metformin at the target doses that doctors often seek. Some population studies have also shown that treatment with Metformin is associated with a lower risk of developing cancer.
When a patient starts treatment with Metformin, you usually start with two tablets a day, preferably with meals such as lunch and dinner, usually starting with a strength of 500 mg. The tablet strength can be increased to 850-1,000 mg after a few weeks if the person tolerates the treatment well. It is common for gastrointestinal side effects to prevent increase in doses.
For those of you who use Metformin
Various tips to reduce the risk of the feared complication of lactic acidosis in metformin therapy are to be careful with treatment for people with impaired renal function, to avoid situations leading to drying. Caution should also be exercised during treatment with antiinflammatory drugs (NSAIDs), antihypertensive drugs (ACE inhibitors/ARB) and when co-administered with the new blood sugar lowering agent SGLT2 inhibitors
Before you are using Metformin, you should tell your doctor or dentist about all the products you are using. People who eat Metformin may pause treatment for a short period to undergo the examination and then resume treatment a few days after the examination.
Limit alcohol while using this medicine because it may increase the risk of lactic acidosis and blood sugar drop. In case of high fever, the use of diuretics, excessive sweating, diarrhoea or vomiting, the body loses a lot of fluid and the risk of lactic acidosis increases.
Before you take Metformin
If you are allergic to Metformin or have other allergies, you should inform your doctor about this. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more information. It can be more difficult to control your blood sugar when your body is stressed (for example, due to fever, infection, injury or surgery). Consult your doctor as increased stress may require a change in your treatment plan, medication or blood sugar testing.
Older adults may be at greater risk of side effects such as low blood sugar or lactic acidosis. During pregnancy, this medication should be used only when necessary. Discuss the risks and benefits of your doctor. Your doctor may suggest using insulin instead of this product during pregnancy. Metformin can cause changes in the menstrual cycle (promote ovulation) and increase the risk of becoming pregnant. Consult your doctor or pharmacist about the use of reliable contraception when using this medication. Metformin passes into breast milk in small amounts. Consult your doctor before breastfeeding.
Effect on children and adolescents
Few studies have investigated the effectiveness of Metformin use in children and found that these showed the same improvements in blood sugar metabolism as in adults.
Sulfonylurea and Meglitinides
Sulfonylurea and Meglitinides are two groups of medicines used to treat type 2 diabetes and the medicines are taken with food intake. These two treatments are considered to be secondary in the treatment of type 2 diabetes, which means that people who cannot tolerate Metformin due to side effects or other diseases that are contraindicated to Metformin should try a treatment from this group of medicines. The recommended preparations are Glibenclamide, Glimepiride or Repaglinide. SU preparations have been on the market since the 1950s and have previously been dominant in tablet treatment of type 2 diabetes. These drugs often have a good effect in the first five to ten years and may lower long-term blood sugar (HbA1c) in the order of 1 — 1.5%, equivalent to 10 — 15 mmol/mol HbA1c.
How do SU preparations and Meglitinides work
Medicinal products belonging to these groups have a similar mechanism of action which is different from other tablet treatments in type 2 diabetes. They improve blood sugar levels by stimulating our own pancreatic insulin producing cells to secrete more insulin. Insulin is the body’s own hormone that allows our cells to absorb sugar (glucose), which means that blood sugar levels decrease as insulin levels increase blood circulation. The effectiveness of these drugs depends largely on the functioning of our insulin-producing beta cells and how much insulin they still contain.
These drugs are rapidly absorbed from the gastrointestinal tract into the bloodstream and stimulate pancreatic cells relatively quickly, already after 30 minutes there is an increase in insulin levels in the blood and a decreasing effect on blood sugar levels. As with Sulfonylurea, Meglitinides work by stimulating insulin release. Meglitinides are taken primarily for meals because the duration of action of the drug is short. During food intake, the hormone insulin is released into the blood circulation, therefore the physiological insulin response is enhanced when the drug is taken with food.
The effectiveness of Sulfonylurea is similar to that observed with Metformin, however, the medicine is more difficult to set and at higher levels the risk of serious blood sugar falls (hypoglycaemia) increases. Glimepiride and Glibenclamide tend to achieve their maximum blood sugar lowering effect at relatively low doses. Some studies suggest that SU preparations are better at preventing myocardial infarction but have a higher risk of serious blood sugar falls compared to Metformin.
Brief information on the mechanisms of action of these drugs
- Increases the secretion of the remaining insulin in the body, as a result decreases sugar levels in the blood.
- Medicines work better if used during meals, it enhances the body’s own insulin secretion that occurs during food intake
- Studies show that SU preparations have the ability to enhance our Sensitivity of cells to the hormone insulin
- After a few years, the effect of treatment with these drugs decreases. This is probably due to a successive loss of insulin-producing beta cells, which occurs in type 2 diabetes. A fatigue of the beta cells may be another factor.
In Sweden there is a medicine called Repaglinide, which belongs to the group Meglitinides. The blood sugar lowering effect of this medicine is similar to that seen with Metformin and other tablet therapies. Repaglinide has the advantage that people with impaired renal function can take this drug without the risk of its accumulation in the body. Repaglinide has a short duration of action and is taken into meals 1 to 4 times daily.
Clinical effects of SU preparations and Meglitinides
Drugs belonging to the Sulfonylurea and Meglitinides group may be used as first-choice treatment for newly onset people with type 2 diabetes. However, this is particularly relevant for people where treatment with Metformin is risky (for example, in individuals with severe renal failure). At present, it is much more common for individuals with type 2 diabetes to be offered these drugs as an add-on to Metformin.
Some studies show that SU preparations have the ability to enhance the ability of our insulin-producing beta cells to record sugar levels in the blood. Beta-cells of the pancreatic gland work almost like a thermostat in the body, their task is to sense insulin and sugar levels instead of temperature. In type 2 diabetes, beta cells are believed to lose some of their ability to sense insulin and sugar levels in the blood, resulting in it becoming more difficult to regulate insulin secretion and blood sugar levels. Other studies also show that our cells are better at handling insulin when using SU preparations.
Side effects and general advice for those who use these drugs
Weight gain is a well-known side effect of Sulfonylurea and studies have seen an average weight gain of about 3 kg.10 It should be noted that these medicines can cause a fall in blood sugar (hypoglycaemia).
If you use Sulfonylurea, you should not skip meals. This is because the medicine stimulates beta cells to excrete insulin, especially during food intake. Beta-cells release low doses of insulin continuously, but in connection with food intake, beta cells inject insulin, the phenomenon looks like clear nail tags that are activated for a short period before it returns to secrete low levels continuously.
If you skip meals, your blood sugar level may go too low (hypoglycaemia). You need to stick to a meal schedule – and eat even if you are not hungry – to make sure that the insulin ejected from the beta cells has enough blood sugar to use for the whole day, otherwise there is a risk of falling blood sugar.
If you forget to take your medicine and it’s been more than 2 hours since you should have taken the dose, skip it and take the next tablet when the time comes. This is especially true for those who have SU preparations or Meglitinides in combination with another drug for type 2 diabetes. If SU is the only medicine prescribed (monotherapy) for type 2 diabetes, no dose should be missed unless it is too close to the next dose.
People who use these medicines can lose weight, the reason for this is that the person must eat even if you are not hungry while taking Sulfonylurea or Meglitinides. If your blood sugar levels are low, even if you eat regular meals and take the medicine as prescribed, talk to your healthcare professional about adjusting your medication or consider possible causes of low blood sugar.
Sulfonylurea is very effective, but, as with any medicine, there are pros and cons of taking them. Up to 20% of people taking these drugs will not respond to them, possibly the proportion of people with type 2 diabetes who have no insulin left in the pancreas. For some other people, these drugs can work initially, but over time they become less effective.
Brief information on the side effects of these drugs
- Sudden blood sugar drops (hypoglycemia), sometimes prolonged and even life-threatening.
- The clinical picture of hypoglycaemia with these preparations usually resembles a stroke
- Light weight gain (nausea and vomiting)
- Sensitive and rash
It is important that you regularly check your blood sugar levels when you are taking a Sulfonylurea. Make sure you know the signs and symptoms of low blood sugar (dizziness, trembling, sweating, headache, hunger) and how to treat it (take 15 grams of carbohydrates, such as 3-4 sugar tablets or 4 cups juice, wait 15 minutes to check your blood sugar and treat again if it still is low). If you usually have low blood sugar, let your doctor know. You may need a lower dose. Your skin may be more sensitive to sunlight while using these medicines. Be sure to use enough sun protection.
The safety of using SU preparations during pregnancy has not been established. If you plan to become pregnant while taking Sulfonylurea, contact your healthcare provider immediately so that the right medication can be prescribed.
How does Akarbos work
Akarbose is another type 2 diabetes medicine that is not as common as Metformin, SU preparations or Meglitinides. The drug acts locally in the intestine and works by inhibiting a protein in the intestine called alpha-glucosidase. This protein has the task of breaking down large sugar molecules in the gastrointestinal tract to simplify the absorption of sugar into the bloodstream.
Since Akarbose prevents the breakdown of large sugar molecules in the intestine, it is taken with food intake because it reduces the absorption of sugar in the intestine. This means that the medicine specifically targets increases in blood sugar that occur after food intake (post-prandial glycaemia).
Akarbose is a possible secondary option in the treatment of type 2 diabetes. However, the drug Glucobay may be offered to patients in combination with Metformin, Sulfonylurea and insulin. Akarbose is best suited to obese or obese individuals because it is weight-neutral, even elderly patients with newly discovered type 2 diabetes may be suitable for treatment with Akarbose.
Akarbose has been shown to be less effective than Metformin and other tablet treatments in type 2 diabetes, but does not pose a risk of severe blood sugar falls (hypoglycaemia), in addition, only small concentrations of the drug are absorbed into the blood circulation, mostly active in the digestive tract. intestinal tract. The medicine may be taken even in case of impaired renal function and the dose does not need to be adjusted for this reason. Some studies indicate that treatment with Akarbose may reduce the risk of heart attack and hypertension (hypertension).
Brief information about this drug
- Akarbose works by inhibiting proteins in the gastrointestinal tract called alpha-glucosidase, this leads to a delayed absorption of sugars from food.
- Akarbose provides improved metabolic control as measured by a decrease in long-term blood sugar (HbA1c)
- Most common side effects are gastrointestinal disorders
Side effects and general advice about Akarbos
The drug can cause side effects from the gastrointestinal tract and its use is most often limited by this. Common side effects are flatulence (meteorism), abdominal pain, flatulence and sometimes even diarrhoea. These side effects usually decrease with time. If side effects last for a long time, consult your doctor.
To reduce the risk of gastrointestinal side effects, a low starting dose of 50 mg, 1 tablet every day is recommended, therefore increasing the dose slowly to detect the optimal dose for each individual, the maximum dose is 100 mg tablets, 3 times each day.
People with any form of inflammatory bowel disease (IBD), intestinal ulcers, intestinal obstruction or other conditions that may worsen due to increased gas formation in the intestine should not use medicines from the group of Akarbos. Akarbose does not normally cause blood sugar drops (hypoglycaemia). Low blood sugar may occur if this medicine is prescribed with other medicines for diabetes.
|Adverse Efficacy Profile and Efficacy for Metformin, Sulfonylurea, Meglitinides and Akarbos|
|Drug||Weight increase||Blood sugarfall (hypoglycaemi)||Gastrointestinal side effects||Effects on blood sugar (HbA1c)|
|Metformin||–||–||+ +||+ + +|
|Sulfonylurea||+ +||+ +||–||+ + +|
|Meglitinider||+ +||+ (+)||–||+ + +|
|Akarbos||–||–||+ + +||+|
Glitazones, also called Thiazolidinediones, are a group of medicines that improve metabolic control in people with type 2 diabetes, which means they get better blood glucose levels. The medicines are called Pioglitazone and Rosiglitazone, both of which are treatment options for type 2 diabetes. The medicine is usually taken 1 to 2 times daily.
How does Glitazones work
These drugs act by inhibiting a protein in the body called PPAR gamma. This protein is found in all cells and therefore most likely has an effect on many of the body’s organs and functions, but they are especially found in adipose tissue. Protein activates a number of genes in the body and plays an important role in how the body handles sugar and how it stores fat. The drug acts mainly on various genes in adipose tissue, liver tissue and musculature.
The drug has beneficial effects on sugar and blood fat metabolism, in addition, the drug improves the sensitivity to insulin in the tissues of the body, i.e. reduces insulin resistance. In addition to this, various studies show that the medicine may have a positive effect against another condition called liver greasing. This condition is often observed in people with type 2 diabetes and implies increased storage of fat in the liver, remember that a lot of fat in the liver is dangerous and contributes to the development of type 2 diabetes and several other chronic diseases.
Glitazones help lower blood pressure and improve blood fat metabolism by increasing the levels of healthy fat HDL cholesterol. Research also shows that these drugs have a positive effect on vascular function and other factors. The effect of these drugs comes gradually and appears only four to eight weeks after initiation of therapy, the drug leads to a marked decrease in long-term blood sugar (HbA1c) from approximately 0.8 to 1.5 percentage points, which is comparable to the decrease observed with treatment with Sulfonylurea, DPP4 inhibitors and Metformin.
These medicines are often given in combination with Metformin or Sulfonylurea which leads to a stronger decrease in long-term blood sugar (HbA1c). Treatment with these drugs has shown in large clinical trials about 18% lower risk of cardiovascular disease, most antidiabetic drugs that have shown a significantly lower risk of complications usually lie in this magnitude between 10-20% lower risk.
Briefly about side effects and general advice on the use of Glitazones
In some studies, however, it has been noted that the preparations increase the risk of developing a cardiac complication called heart failure, i.e. when the pumping capacity of the heart is impaired. If the drug is administered to people with heart failure, it can lead to aggravation of heart failure further and therefore the use of these preparations is not recommended at all degrees of heart failure. Drug studies showed that people who eat Glitazones also gain weight on average 1-5 kg. The risk of blood sugar fall (hypoglycemia) is low
The Glitazones group is also associated with an increased risk of skeletal fractures than other tablet treatment for type 2 diabetes, this was observed in the Adopt study which reported more cases of bone fractures in women treated with Rosiglitazone compared to women treated with Metformin or Sulfonylurea.
People with liver damage or elevated liver proteins (transaminases) should avoid treatment with Pioglitazone and patients using the product should regularly monitor their liver values.
A new group of drugs for the treatment of type 2 diabetes called GLP-1 analogues (glucagon-like peptide-1) was introduced a few years ago. The drug mimics the bodily hormone GLP-1, a hormone that is released from the intestine and belongs to the group of incretins. These drugs have positive metabolic effects on the body. DPP4 inhibitors are another group of drugs discussed in a separate article, but as curious it has been shown to reduce the degradation of the body’s GLP-1, which is positive because the concentrations of GLP-1 rise and exert an even greater positive metabolic effect. The medicine can be administered to patients with impaired renal function and has several positive effects in addition to the blood-sugar-lowering effect.
How do GLP-1 analogues work
These drugs work by increasing the secretion of insulin (especially after meals) just like SU preparations and Meglitinides, GLP-1 analogues achieve this through a completely different process. Using GLP-1 analogues reduces the amount of sugar that the liver produces, this in turn reduces blood sugar levels. GLP-1 also reduces the secretion of the hormone glucagon from the pancreas. Glucagon is a hormone that has the task of increasing sugar levels in the blood, which means that higher levels of the hormone GLP-1 result in less secretion of the hormone Glucagon. Also it leads to lower blood sugar levels in the body. In addition, gastric emptying is slowed down, which leads to a previous feeling of satiety and reduced food intake.
Briefly about the mechanisms of action of this drug
- GLP-1 is a hormone released from the gastrointestinal tract after meals. The release depends on how large amounts of sugar are available in the gastrointestinal tract and the bloodway.
- GLP-1 binds to specific receptors on insulin-producing beta cells (and also alpha cells to some extent). This potentiates the stimulating effect of sugar on insulin release from the beta cells.
- GLP-1 acts appetite suppressing. This may be due to both the effects in the brain and the slowing of gastric emptying.
- In animal experiments, positive effects on the total mass of beta cells have also been observed, but human data are not available.
What are the clinical effects of GLP-1 analogues
GLP-1 analogues lower on average HbA1c by 10 mmol/mol. Several studies have shown that GLP-1 analogues have a weight reducing effect, but the effect differs between the different drug preparations, two drugs called Liraglutide and Exenatide have the greatest weight reducing effect.
Exenatide is a preparation belonging to the class of GLP-1 analogues and is currently used in the treatment of type 2 diabetes in combination with Metformin and/or Sulfonylurea in patients who have not received adequate glucose control from these medicines.
Currently, few studies have shown that GLP-1 analogues can be administered to individuals with type 1 diabetes and lead to further blood sugar reduction.
So far, GLP-1 analogues are used less than Metformin and SU preparations. GLP-1 analogues are injection drugs and are taken by syringe in the subcutaneous fat just like insulin. Victoza and Luxumia are two different GLP-1 analogues that are taken 1 time per day, while Byetta is taken 2 times a day and Bydureon as well as Trulicity are taken once a week. The use of GLP-1 analogues increases. The first long-term studies published (Lytumia and Victoza) proved to be safe preparations from a cardiovascular perspective, and the Victoza study not only showed that it was safe to use from a cardiovascular perspective, but it also has beneficial effects on cardiovascular disease and death.
What to consider if you use GLP-1 analogues
Before injecting each dose, clean the injection site. Change the injection site almost every time to reduce the impact on the skin. Inject the medicine under the skin of the thigh, abdomen or upper arm, usually twice daily. The injection should be over 60 min before meals.
Since GLP-1 analogues slow down digestion in the stomach, some medicines (such as birth control pills, antibiotics taken in the mouth) may not work as well if you take them at the same time. Take birth control pills or antibiotics for at least 1 hour before using GLP-1 analogues. If you have to take these medications with food, take them with a meal or snack when you do not take GLP-1 analogues.
At present, patients with type 1 diabetes, children, pregnant, lactating women or patients with severe renal failure are not recommended to start treatment with GLP-1 analogues. Side effects such as nausea, vomiting, diarrhoea, nervousness and loss of appetite are common but often transient with these medicines, the risk of side effects is reduced if the attending physician increases the dose to the target dose slowly. There are even few cases of pancreatic inflammation (pancreatitis), this condition manifests itself in the form of severe abdominal pain, with nausea and vomiting.
How does DPP4 inhibitors work
DPP4 inhibitors are a group of drugs that act by inhibiting a protein in the body called dipeptidyl peptidase-4, hence the name of DPP4 inhibitors. The drug leads to a higher concentration of the hormone GLP-1, which in turn causes a positive blood sugar lowering effect. GLP-1 leads to the release of the hormone insulin while slowing the secretion of glucagon (a hormone whose task is to raise blood sugar levels). Remember that glucagon causes the production of sugar from the liver, and insulin makes it possible to absorb sugar from the blood circulation to each cell. When treated with DPP4 inhibitors alone, it is observed that HbA1c falls on average by 5-10 mmol/mol.
Side effects and general advice when using these drugs
The drug is considered weight neutral and can be used in renal impairment. The drug is often used in conjunction with Metformin and is considered safe from a cardiovascular perspective, in addition, no blood sugar drops (hypoglycaemia) have been reported. Several combination preparations with Metformin and DPP4 inhibitors are available.
DPP4 inhibitors are associated with various side effects depending on the preparation used. The side effects that may occur are infections of the throat and throat, headache and urinary tract infections
|Tablets and drug groups in type 2 diabetes|
|Mechanism of action||Generic name||Product name|
|Drugs that stimulate insulin resistance||Glimepiride, Repaglinide
|Glibenklamid, Daonil, Euglucon, Mindiab, Glibenese, Apamid, Ozidia, Glimepiride, Amaryl, Repaglinide, NovoNorm|
|Drugs that increase insulin sensitivity||Metformin||Metformin, Glucophage|
|Drugs that delay carbohydrate uptake||Akarbos||Glucobay|
|GLP-1 drugs||Exenatide, Lixisenatide,|
|Byetta, Bydureon, Lyxumia|
|Drugs that increase glucose elimination via urine||Dapagliflozin, Kanagliflozin|
|Forxig, Invokana, Jardiance|
There is a new group of drugs for people with type 2 diabetes called SGLT2 inhibitors, which work by increasing the excretion (filtration) of sugar (glucose) by the kidneys. The kidneys have the task of filtering the blood and excrete some of the sugar contained in the blood into the urine, but some of the sugar is reabsorbed from the kidneys into the bloodstream.
How does SGLT2 inhibitors work?
SGLT2 inhibitors work by inhibiting the receptor responsible for the reuptake of sugar to the bloodstream in the kidney, resulting in lower levels of blood sugar because the individual secretes large portions of the sugar through the urine, other benefits are that excess fluid is excreted and it can also cause weight loss.
What results are seen in treatment with SGLT2 inhibitors?
Studies show that people with type 2 diabetes who use any type of this drug lose weight, about 1.5 — 2 kg and sometimes even more. The first drug from this group was launched in 2015 and therefore our knowledge of long-term effects and side effects is limited. SGLT2 inhibitors reduce long-term blood sugar by 10-15 mmol/mol.
However, the studies published have shown convincing results regarding the positive effects of the drug on the body’s blood circulation and sugar metabolism. In people treated with SGLT2 inhibitors, it was observed that the risk of heart failure was 20% lower and the risk of heart failure worsening in people with the disease decreased sharply.
There are several combination drugs with SGLT2 inhibitors and Metformin. Because the drug causes fluid loss, it is important that patients with ongoing diuretic therapy and SGLT2 inhibitors should be cautious in conditions leading to greater fluid loss such as fever, infection, dehydration, etc.
Patients included in the drug studies with SGLT2 inhibitors were type 2 diabetics with previous cardiovascular disease. Students then received either SGLT2 inhibitors in addition to other diabetes treatment or Placebo in control patients. All studies investigating SGLT2 inhibitors have demonstrated a convincing effect on cardiovascular diseases and death. The drug has the greatest effect on the outcome of heart failure, and the reason is believed to be increased urine output, which leads to fluid not accumulating in the circulation and thus much less burdens the heart. Nowadays there are several combination preparations with SGLT2 inhibitors and Metformin.
Drugs belonging to the class of SGLT2 inhibitors
|Generic name||Trading name|
Side effects in treatment with SGLT2 inhibitors
However, the drug causes more urinary tract infections and fungal infections in the lower urinary tract because the concentration of sugar increases in the bladder, which promotes bacterial and fungal growth. This can be problematic for many patients who experience recurrent infections and, in some cases, even stop treatment precisely for this reason. As a rule, the drug does not cause blood sugar drops (hypoglycemia). At present, individuals with severe renal failure are not recommended to use SGLT2 inhibitors although some studies suggest that the medicine has a positive effect on kidney function.
If you use SGLT2 inhibitors with insulin, sulfonylurine or glinides, the risk of hypoglycemia may increase. There are also several reported cases that these drugs cause another feared metabolic complication called diabetes ketoacidosis, this means that ketones accumulate in the body.
References: treatment of type 2 diabetes
- Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-2559. doi:10.1056/NEJMoa0802743.
- ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-2572. doi:10.1056/NEJMoa0802987.
- Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-139. doi:10.1056/NEJMoa0808431.
- Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-1589. doi:10.1056/NEJMoa0806470.
- Turner RC, Millns H, Neil HA, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998;316(7134):823-828.
- Stratton IM, Cull CA, Adler AI, Matthews DR, Neil HAW, Holman RR. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia. 2006;49(8):1761-1769. doi:10.1007/s00125-006-0297-1.
- Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. In: Vol 32. American Diabetes Association; 2009:193-203. doi:10.2337/dc08-9025.
- Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854-865.
- DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med. 1995;333(9):541-549. doi:10.1056/NEJM199508313330902.
- Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147(6):386-399.
- Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016;374(11):1094-1094. doi:10.1056/NEJMc1600827.
- Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720.
- Marx N, McGuire DK. Sodium-glucose cotransporter-2 inhibition for the reduction of cardiovascular events in high-risk patients with diabetes mellitus. Eur Heart J. May 2016. doi:10.1093/eurheartj/ehw110.
- Sattar N, McLaren J, Kristensen SL, Preiss D, McMurray JJ. SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms? Diabetologia. April 2016:1-7. doi:10.1007/s00125-016-3956-x.