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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
  1. Steve Kanters1,
  2. Lars Wilkinson2,
  3. Hrvoje Vrazic2,
  4. Rohini Sharma1,
  5. Sandra Lopes2,
  6. Evan Popoff1,
  7. Eric Druyts1
  1. 1 Precision Xtract, Vancouver, British Columbia, Canada
  2. 2 Novo Nordisk A/S, Søborg, Denmark
  1. Correspondence to Steve Kanters; skanterz{at}gmail.com

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.

  • once-weekly semaglutide
  • type 2 diabetes
  • glucagon-like peptide-1 analogue
  • sustain clinical trial programme
  • SGLT-2 inhibitors

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors SK, EP, ED, LW, HV and SL participated in the conception and design of the work. SK, EP and ED participated in the collection of data. All authors participated in data analysis and interpretation. SK, RS, ED, LW, HV and SL were responsible for drafting the paper. All authors were involved in the critical revision of the paper, and all authors also gave final approval for this version of the paper to be published.

  • Funding This work was supported by Novo Nordisk A/S. No restrictions have been placed on the choice of analyses or the interpretation of the results.

  • Competing interests LW, HV and SL are employees of Novo Nordisk. RS, EP, ED and SK report funding provided by Novo Nordisk to Precision Xtract, where they are employees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data used for these analyses are publicly available. Given the use of clinical Study Reports, data are not available. For further questions regarding data, please reach out to the corresponding author.

  • Patient consent for publication Not required.

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