Aim To compare the effects of glucose‐lowering drugs on body weight and blood pressure in adults with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library, and grey literature sources until 29 September 2020 for randomized controlled trials of at least 24 weeks' duration assessing the effects of glucose‐lowering drugs on body weight and blood pressure in adults with type 2 diabetes. We performed frequentist network meta‐analyses and calculated weighted mean differences and 95% confidence intervals combining trial arms of different approved doses of a given intervention into a single group. We evaluated the confidence in pooled estimates using the CINeMA (Confidence In Network Meta‐Analysis) framework. Results In total, 424 trials (276 336 patients) assessing 21 antidiabetic medications from nine drug classes were included. Subcutaneous semaglutide was the most efficacious in reducing body weight followed by oral semaglutide, exenatide twice‐daily, liraglutide, and the sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin. The same agents also conferred the greatest reductions in systolic blood pressure. Metformin had a modest effect in reducing body weight and systolic blood pressure. Diastolic blood pressure was reduced with the SGLT‐2 inhibitors pioglitazone, exenatide twice‐daily and semaglutide. In subgroup analyses of trials with over 52 weeks' duration, semaglutide and SGLT‐2 inhibitors reduced both body weight and systolic blood pressure. Conclusions Semaglutide and SGLT‐2 inhibitors conferred reductions both in body weight and blood pressure that were sustainable for over 1 year of treatment. These agents may be preferable treatment options for patients with type 2 diabetes who are overweight/obese and/or hypertensive.

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Purpose There is controversy regarding the optimal statistical method to interpret how robust is a statistically significant result. The fragility index (FI) and the reverse fragility index (RFI) are quantitative measures that can facilitate the appraisal of a clinical trial’s robustness. This study was performed to evaluate the FI and RFI of randomized controlled trials (RCTs) examining nutritional interventions in patients with diabetes mellitus, focusing on cardiovascular outcomes. Methods A systematic search was conducted and relevant RCTs were identified in three databases. RCTs examining nutritional interventions (supplements or dietary patterns) in patients with DM with dichotomous primary endpoints involving cardiovascular outcomes were eligible. Data were extracted to compose 2 × 2 event tables and the FI and RFI were calculated for each comparison, using Fisher’s exact test. Risk of bias (RoB) of the included RCTs was assessed with the Cochrane RoB 2.0 tool. Results A total of 14,315 records were screened and 10 RCTs were included in the analyses. The median FI of the paired comparisons was 3 (IQR: 2–4) and the median RFI was 8 (IQR: 4.5–17). RoB and heterogeneity were low. Conclusions RCTs examining nutritional interventions and cardiovascular outcomes among patients with diabetes mellitus appear to be statistically fragile. Τhe FI and the RFI can be reported and interpreted as an additional perspective of a trial’s robustness. Highlights • In the evidence-healthcare era, assessing how robust statistically significant results are remains a matter of controversy. • Recently, the fragility index (FI) and reverse fragility index (RFI) were proposed to assess the robustness of randomized controlled trials (RCTs) with 2 × 2 comparisons. • When applying the FI and RFI, RCTs examining nutritional interventions and cardiovascular outcomes among patients with diabetes mellitus (DM) appear to be statistically fragile. • Τhe FI and the RFI can be reported and interpreted as an additional perspective of a trial’s robustness. • RCTs implementing nutrition interventions among patients with DM can improve their methodology.

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