Dataset Information

Comparative efficacy of once-weekly semaglutide versus SGLT-2 inhibitors in patients inadequately controlled with one to two oral antidiabetic drugs: a systematic literature review and network meta-analysis.

ABSTRACT:

Objective

To determine the comparative efficacy of once-weekly semaglutide relative to sodium-glucose cotransporter 2 inhibitors (SGLT-2is) licensed in Europe and North America among patients with type 2 diabetes (T2D) inadequately controlled with 1-2 oral antidiabetics (OADs), using a network meta-analysis (NMA). Design systematic review and network meta-analysis. Data Sources EMBASE, MEDLINE and CENTRAL were searched from January 1994 to August 2017.

Methods

Randomised controlled trials with ≥20 weeks of treatment evaluating once-weekly semaglutide or SGLT-2is. Primary outcomes included change from baseline in: HbA1c, weight, systolic blood pressure, postprandial blood glucose and fasting plasma glucose. Fixed-effect and random-effect Bayesian NMA were used to indirectly compare treatment effects at 26 (±4) weeks. Metaregression and sensitivity analyses were conducted. Model selection was performed using the deviance information criterion and consistency was assessed by comparing indirect (edge-splitting) to direct evidence.

Results

Forty-eight publications representing 21 trials were included. The mean differences (MD) in change from baseline in HbA1c of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from -0.56% for canagliflozin 300 mg (95% credible interval (CrI): -0.76 to -0.33%), to -0.95% for dapagliflozin 5 mg (95% CrI: -1.20 to -0.69%). The MD in change from baseline in weight of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from -1.35 kg for canagliflozin 300 mg to -2.48 kg for dapagliflozin 5 mg, while change from baseline in fasting plasma glucose ranged from -0.41 mmol/L for canagliflozin 300 mg to -1.37 mmol/L for dapagliflozin 5 mg. Once-weekly semaglutide was not statistically differentiable than all SGLT-2is in reducing systolic blood pressure. NMA was not feasible for postprandial blood glucose and safety outcomes.

Conclusion

Once-weekly semaglutide demonstrated statistically significant and clinically meaningful reductions in HbA1c and body weight in T2D patients inadequately controlled with 1-2 OADs compared to all SGLT-2is licensed in Europe and North America.

SUBMITTER: Kanters S

PROVIDER: S-EPMC6661926 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AIMS:To assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D). METHODS:In this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0?mg) or once-daily oral sitagliptin 100?mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30?weeks. RESULTS:Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5?mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0?mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0?mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5?mg, semaglutide 1.0?mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0?mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P?<?.0001). Body weight (baseline 69.3?kg) was reduced by 2.2 and 3.9?kg with semaglutide 0.5 and 1.0?mg, respectively (ETD -2.22?kg, 95% CI -3.02; -1.42 and -3.88?kg, 95% CI -4.70; -3.07; both P?<?.0001). CONCLUSIONS:In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.