Clinician Article
Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis.
PMID: 27059700
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EndocrineRelevance - 7/7
Newsworthiness - 5/7 -
Family Medicine (FM)/General Practice (GP)Relevance - 6/7
Newsworthiness - 4/7 -
General Internal Medicine-Primary Care(US)Relevance - 6/7
Newsworthiness - 4/7 -
Internal MedicineRelevance - 4/7
Newsworthiness - 5/7 -
CardiologyRelevance - 4/7
Newsworthiness - 4/7
Abstract
AIM: To assess the comparative efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors in adults with type 2 diabetes.
METHODS: We electronically searched randomized controlled trials (=24 weeks) including canagliflozin, dapagliflozin or empagliflozin that were published up to 3 November 2015. Data were collected on cardiometabolic and safety outcomes and synthesized using network meta-analyses.
RESULTS: A total of 38 trials (23 997 participants) were included. Compared with placebo, all SGLT2 inhibitors reduced glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and blood pressure, and slightly increased HDL cholesterol. Canagliflozin 300 mg reduced HbA1c, FPG and systolic blood pressure and increased LDL cholesterol to a greater extent compared with other inhibitors at any dose. At their highest doses, canagliflozin 300 mg reduced: HbA1c by 0.2% [95% confidence interval (CI) 0.1-0.3] versus both dapagliflozin 10 mg and empagliflozin 25 mg; FPG by 0.6 mmol/l (95% CI 0.3-0.9) and 0.5 mmol/l (95% CI 0.1-0.8) versus dapagliflozin and empagliflozin, respectively; and systolic blood pressure by 2 mmHg (95% CI 1.0-3.0) versus dapagliflozin; and increased LDL cholesterol by 0.13 mmol/l (95% CI 0.03-0.23) and 0.15 mmol/l (95% CI 0.06-0.23) versus dapagliflozin and empagliflozin, respectively. The highest doses of inhibitors had similar effects on body weight reduction. Canagliflozin 300 and 100 mg increased the risk of hypoglycaemia versus placebo, dapagliflozin 10 mg and empagliflozin 10 mg [odds ratios (ORs) 1.4-1.6]. Dapagliflozin 10 mg increased the risk of urinary tract infection versus placebo and empagliflozin 25 mg (ORs 1.4). All inhibitors similarly increased the risk of genital infection (ORs 4-6 versus placebo).
CONCLUSIONS: Although they increase the risk of genital infection, SGLT2 inhibitors are effective in improving cardiometabolic markers in type 2 diabetes, with canagliflozin 300 mg performing better in this respect than other inhibitors. Further studies will clarify whether these differences are likely to translate into differing long-term outcomes.
Clinical Comments
Endocrine
This good meta-analysis of 38 trials with SGLT2 inhibitors shows the overall efficacy of the class at reducing HbA1c, weight and BP. It shows that canaglifozin is more effective than either dapaglfiozin or empaglfozin. The benefit of the class is offset by an increased risk for genital infections.
Endocrine
This is probably the first of this kind of study where 3 approved SGLT2 receptor inhibitors were compared. Although this study should have a good clinical implication, further trials are required to find superiority of one SGLT2 receptor antagonists over other. Physician should also keep in mind the increased risk of toe amputation (Ref: Canagliflozin Cardiovascular Assessment study; CANVAS) due to use of canagliflozin, specifically in patients with heart and vascular disease and also should keep an eye on ongoing CANVAS-R trial.
Internal Medicine
The authors have chosen to evaluate the biochemical effects of a new therapeutic approach for type 2 diabetes. Quite unfortunately there is no mention of clinical data. One of their findings is that HbA1c levels decreased by less than 1%. In their design, the authors included several sources of data but failed to describe the basic biochemical characteristics of each laboratory method. Without knowledge of the intra- and inter-assay variation this conclusion is questionable. It follows that the conclusion also is questionable. Doing medical work is taking care with living people, and not just a biochemical evaluation. While the study appeared to me to be interesting, at the end it lost clinical relevance.
Internal Medicine
In the UK, most cardiologists would leave the choice of diabetic medication to general practitioners and endocrinologists. It's useful to know that these medications exist and may be of benefit from a cardiovascular perspective, but I don't think this sort of article is top of a cardiologists reading list. Furthermore, the benefits are theoretical and hard outcome data, such as mortality, is not included, meaning that it is of interest only. Nonetheless, the article is educational and informative and of a high standard. If I needed to take an SGLT2 inhibitor, I would turn to this article for information.
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