The impact of pharmacological and lifestyle interventions on body weight in people with type 1 diabetes: A systematic review and meta-analysis

Aim To systematically review the effects of pharmacological and lifestyle interventions on body weight as a secondary outcome in people with type 1 diabetes. Methods The Ovid Medline, Embase and Cochrane Library databases were searched for relevant pharmacological (glucagon-like peptide-1 [GLP-1] receptor agonist, sodium-glucose co-transporter-2 [SGLT-2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor and metformin) and lifestyle intervention studies (diet and exercise) for adults with type 1 diabetes reporting body weight change and HbA1c published from January 2000 to May 2020. Meta-analyses were performed for 16 randomized controlled trials (RCTs). Results Thirty-three RCTs (n = 9344 participants), 26 pharmacological (on average 43.9 years, 83.1 kg, HbA1c 8.1%; 55.8% male) and seven lifestyle-based interventions (on average 37.0 years, 85.0 kg, HbA1c 8.1%; 84.6% male), were analysed. The GLP-1 receptor agonist liraglutide 0.6 mg (mean difference [MD]: –2.22 kg [95% CI: –2.55 to –1.90]), 1.2 mg (MD: –3.74 kg [95% CI: –4.16 to –3.33]) and 1.8 mg (MD: –4.85 kg [95% CI: –5.29 to –4.41]), and the SGLT-2 inhibitors empagliflozin 2.5 mg (MD: –1.47 kg [95% CI: –2.23 to –0.71]), 10 mg (MD: –2.77 kg [95% CI: –3.24 to –2.31]) and 25 mg (MD: –3.06 kg [95% CI: –3.57 to –2.55]) and sotagliflozin 200 mg (MD: –2.40 kg [95% CI: –2.87 to –1.94]) and 400 mg (MD: –3.23 [95% CI: –3.73 to –2.72]) were associated with significant reductions in body weight. No significant effect on body weight was found for DPP-4 inhibitors, other GLP-1-receptor agonists, metformin, or for lifestyle interventions (i.e. exercise and diet). Conclusions In people with type 1 diabetes, several adjuvant pharmacological interventions showed weight reduction as a secondary outcome. Future studies in overweight people with type 1 diabetes are needed to establish whether the lifestyle and pharmacological interventions reviewed here have potential as components of complex interventions aimed at body weight reduction as a primary outcome.