Sodium-glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus

Review question

What are the effects of the group of glucose-lowering drugs called 'sodium-glucose cotransporter (SGLT) 2 inhibitors' for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus?

Background

The SGLT 2 inhibitors (such as canagliflozin, dapagliflozin and empagliflozin) are glucose-lowering drugs that reduce blood glucose levels by increasing the secretion of glucose from the kidneys to the urine. SGLT 2 inhibitors were recently approved for the treatment of diabetes in people with type 2 diabetes mellitus. It is currently not known whether SGLT 2 inhibitors should be prescribed for people with raised blood glucose levels who do not meet the criteria for having type 2 diabetes. We wanted to find out whether these drugs would prevent or only delay the development of type 2 diabetes. Furthermore, we wanted to analyse the effects of SGLT 2 inhibitors on patient-important outcomes such as complications of diabetes (for example kidney and eye disease, heart attacks, strokes), death from any cause, health-related quality of life and side effects of the medications.

Study characteristics

We searched the medical literature and registers of ongoing trials for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) of SGLT 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications. We wanted to synthesise the findings of several studies to answer our review question. Unfortunately, we did not find such a study.

This evidence is up to date as of January 2016.

Key results

We could not include any study in our systematic review. However, we identified two ongoing studies, both evaluating the effects of dapagliflozin in people at risk for the development of type 2 diabetes and a follow-up of 24 to 26 weeks. Both rather short-term studies will mainly report on laboratory outcome measures with some data on side effects and health-related quality of life.

Quality of the evidence

Because we could not include any study we were not able to investigate the quality of the evidence. In both ongoing studies the participants know what kind of medication they are taking which may create problems with the measurement of some outcomes such as health-related quality of life and side effects.

Authors' conclusions: 

Due to lack of data it is not possible to conclude whether SGLT 2 inhibitors prevent or delay the diagnosis of T2DM and its associated complications.

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Background: 

Sodium-glucose cotransporter (SGLT) 2 inhibitors were recently approved as glucose-lowering interventions in people with type 2 diabetes mellitus (T2DM). Potential beneficial or harmful effects of SGLT 2 inhibitors in people at risk for the development of T2DM are unknown.

Objectives: 

To assess the effects of SGLT 2 inhibitors focusing on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose or moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of ongoing for information about additional trials. The date of the last search of all databases was January 2016.

Selection criteria: 

Randomised controlled trials (RCTs) of any duration comparing SGLT 2 inhibitors with any glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these.

Data collection and analysis: 

Two review authors read all abstracts, assessed quality and extracted data independently. We resolved discrepancies by consensus or the involvement of a third author.

Main results: 

We could not include any RCT in this systematic review. One trial was published in two abstracts, but did not provide separate information of the participants with impaired glucose tolerance, impaired fasting glucose or both. We identified two ongoing trials, both evaluating the effects of dapagliflozin (and metformin) in people at risk for the development of type 2 diabetes and a follow-up of 24 to 26 weeks. Both trials will mainly report on surrogate outcome measures with some data on adverse effects and health-related quality of life.

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