Volume 20, Issue 9 p. 2255-2263
ORIGINAL ARTICLE

Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis

Panagiotis Andreadis MD

Corresponding Author

Panagiotis Andreadis MD

Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

Correspondence

Panagiotis Andreadis, MD, MSc, Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642, Thessaloniki, Greece.

Email: [email protected]

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Thomas Karagiannis MD

Thomas Karagiannis MD

Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Konstantinos Malandris MD

Konstantinos Malandris MD

Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Ioannis Avgerinos MD

Ioannis Avgerinos MD

Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Aris Liakos MD

Aris Liakos MD

Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Apostolos Manolopoulos MD

Apostolos Manolopoulos MD

Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Eleni Bekiari MD

Eleni Bekiari MD

Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

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David R Matthews MD

David R Matthews MD

Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK

Harris Manchester College, University of Oxford, Oxford, UK

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Apostolos Tsapas MD

Apostolos Tsapas MD

Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece

Harris Manchester College, University of Oxford, Oxford, UK

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First published: 13 May 2018
Citations: 73
Funding information No funding was received for this study.

Abstract

Aims

To assess the efficacy and safety of semaglutide, a recently approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) for type 2 diabetes.

Materials and methods

We searched major electronic databases and grey literature sources for randomized controlled trials comparing semaglutide with placebo or other antidiabetic agents. Primary outcome was change from baseline in HbA1c. Secondary endpoints included change from baseline in body weight, blood pressure, heart rate and incidence of hypoglycaemia, gastrointestinal adverse effects, pancreatitis and diabetic retinopathy.

Results

A total of 6 placebo-controlled and 7 active-controlled studies with subcutaneous semaglutide were included. We identified only 1 trial with oral semaglutide. Compared with placebo, subcutaneous semaglutide 0.5 and 1 mg reduced HbA1c by 1.01% (95% CI, 0.56-1.47) and 1.38% (1.05-1.70), respectively. Both doses demonstrated superior glycaemic efficacy compared to other antidiabetic agents, including sitagliptin, exenatide, liraglutide, dulaglutide and insulin glargine. Semaglutide also had a beneficial effect on body weight (mean difference vs placebo −4.11 kg, 95% CI −4.85 to −3.37 for semaglutide 1 mg) and systolic blood pressure. We did not observe increased hypoglycaemia rates with semaglutide; nevertheless, we noted an increased incidence of nausea, vomiting and diarrhoea. Cases of pancreatitis were infrequent and the odds ratio for diabetic retinopathy compared with placebo was 1.32 (95% CI, 0.98-1.77).

Conclusions

Semaglutide is a potent once-weekly GLP-1 RA, significantly reducing HbA1c, body weight and systolic blood pressure. However, it is associated with increased incidence of gastrointestinal adverse events. Results for pancreatitis and retinopathy require further assessment in post-approval pharmacovigilance studies.