Metformin for prevention/delay of type 2 diabetes mellitus | Figure 1

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Metformin for prevention/delay of type 2 diabetes mellitus

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Metformin for prevention/delay of type 2 diabetes mellitus (T2DM) and associated complications in persons at increased risk for development of T2DM

Review question

Is the antidiabetic drug metformin able to prevent or delay the development of type 2 diabetes and its associated complications in people with moderately elevated blood sugar levels?

Background

People with moderately elevated blood sugar levels (often referred to as 'prediabetes') are said to have an increased risk for developing diabetes. Metformin is a blood sugar‐lowering medicine which has been used for a long time to treat people with type 2 diabetes. Type 2 diabetes, also known as adult‐onset diabetes, is the most common type of diabetes and prevents the body from using insulin properly (insulin resistance). Type 2 diabetes can have bad effects on health in the long term (diabetic complications), such as severe eye or kidney disease or 'diabetic feet', eventually resulting in foot ulcers.

We investigated whether metformin can also be used to prevent or delay type 2 diabetes in people at increased risk. We examined the effects of metformin on patient‐important outcomes, such as complications of diabetes, death from any cause, health‐related quality of life and side effects of the drug.

Study characteristics

To be included, people had to have blood sugar levels higher than normal, but below the levels that are used to diagnose diabetes. We found 20 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with a total of 6774 participants. The comparator group consisted of diet and exercise, intensive diet and exercise or another blood sugar‐lowering drug. One study dominated the evidence (48% of the total number of all participants). Twelve studies were performed in China. We only included studies with a treatment duration of one year or more. The treatment duration in the included studies varied from one to five years.

This evidence is up to date as of March 2019.

Key results

Fifteen studies compared metformin against diet and exercise. Eight studies compared metformin against intensive diet and exercise and three studies compared metformin plus intensive diet and exercise against intensive diet and exercise only. When compared to standard diet and exercise metformin slightly reduces or delays development of diabetes. However, when compared to intensive diet and exercise, metformin does not provide an additional benefit in reducing or delaying development of diabetes.

Seven studies compared metformin with another glucose‐lowering drug: three studies compared metformin with acarbose. Three studies compared metformin with a thiazolidinedione (such as pioglitazone). There was neither an advantage or disadvantage when comparing metformin with these drugs with respect to the development of diabetes. One study compared metformin with a sulphonylurea (glimepiride). The trial did not report patient‐important outcomes.

In general, the reporting of serious side effects was sparse. Few participants died and we did not detect a clear difference between the intervention and comparator groups. We also did not detect an advantage or disadvantage of metformin in relation to health‐related quality of life. Our included studies did not report on non‐fatal heart attacks, strokes or complications of diabetes such as kidney or eye disease. Few studies estimated the direct medical costs. When compared to diet and exercise, metformin was more expensive. When compared to intensive diet and exercise, metformin was less expensive.

We identified 11 ongoing studies which potentially could provide data for this review. These studies will add a total of 17,853 participants in future updates of our review.

Future studies should investigate more patient‐important outcomes such as complications of diabetes and especially the side effects of the drugs. We do not know whether 'prediabetes' is just a condition defined by laboratory measurements, or whether it is in fact a real risk factor for diabetes. It is also unknown whether treatment of this condition translates into better patient‐important outcomes.

Certainty of the evidence

All included studies had problems in the way they were conducted or reported.

Read the full Cochrane Review here

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