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

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-...

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Main Authors: Steve Kanters, Lars Wilkinson, Hrvoje Vrazic, Rohini Sharma, Sandra Lopes, Evan Popoff, Eric Druyts
Format: Article
Language:English
Published: BMJ Publishing Group 2019-07-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/7/e023458.full
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author Steve Kanters
Lars Wilkinson
Hrvoje Vrazic
Rohini Sharma
Sandra Lopes
Evan Popoff
Eric Druyts
author_facet Steve Kanters
Lars Wilkinson
Hrvoje Vrazic
Rohini Sharma
Sandra Lopes
Evan Popoff
Eric Druyts
author_sort Steve Kanters
collection DOAJ
description 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.
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spelling doaj-art-2867dc3d607246909f1627a7bdec898f2025-08-20T02:49:05ZengBMJ Publishing GroupBMJ Open2044-60552019-07-019710.1136/bmjopen-2018-023458Comparative 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-analysisSteve Kanters0Lars Wilkinson1Hrvoje Vrazic2Rohini Sharma3Sandra Lopes4Evan Popoff5Eric Druyts6director2 Novo Nordisk A/S, Søborg, Denmark2 Novo Nordisk A/S, Søborg, DenmarkDepartment of Surgery and Cancer, Hammersmith Hospital, London, UK1 Gastroenterology, Unidade Local de Saúde de Coimbra, Coimbra, Portugal1 Precision Xtract, Vancouver, British Columbia, Canada1 Precision Xtract, Vancouver, British Columbia, CanadaObjective 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.https://bmjopen.bmj.com/content/9/7/e023458.full
spellingShingle Steve Kanters
Lars Wilkinson
Hrvoje Vrazic
Rohini Sharma
Sandra Lopes
Evan Popoff
Eric Druyts
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
BMJ Open
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://bmjopen.bmj.com/content/9/7/e023458.full
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