Adding liraglutide to insulin in overweight adults with type 1 diabetes did not significantly lower HbA1c, but it reduced body weight by 6.8 kg, decreased insulin doses, and cut hypoglycemic events by 18%.
-6.8 kg weight loss vs placeboWhile liraglutide missed its primary HbA1c target in type 1 diabetes, the significant weight loss and 18% fewer hypos highlight secondary benefits
What the researchers found
The primary endpoint was not met: HbA1c change did not significantly differ between groups (-0.5% with liraglutide vs -0.3% with placebo; between-group difference -0.2%, p=0.18). However, several clinically meaningful secondary benefits emerged:
- Body weight: -6.8 kg difference favoring liraglutide (p=0.015)
- Bolus insulin: -5.8 IU difference (p=0.023)
- Hypoglycemic events: 18% reduction (incident rate ratio 0.82, p<0.001)
- Heart rate: +7.5 bpm increase with liraglutide (p=0.002)
- Gastrointestinal side effects: nausea 58% vs 10%, dyspepsia 22% vs 2%
Gastric emptying was initially delayed at 3 weeks but normalized by 24 weeks.
Why it matters
Many people with type 1 diabetes are overweight and struggle with blood sugar control despite insulin. While liraglutide didn't improve HbA1c, the significant weight loss, insulin dose reduction, and fewer hypos are clinically meaningful. These findings help define where GLP-1 drugs might and might not help in type 1 diabetes — and set the stage for trials of newer GLP-1 drugs like semaglutide in this population.
How the study worked
Randomized, double-blind, placebo-controlled trial at Steno Diabetes Center, Denmark. 100 patients with type 1 diabetes (HbA1c >8%, BMI >25 kg/m²) were randomized 1:1 to liraglutide or placebo added to existing insulin. Liraglutide was escalated from 0.6 mg to 1.8 mg daily over 2+ weeks. Treatment lasted 24 weeks. Analysis used mixed models for efficacy in the modified ITT population.
What this study cannot tell us
The sample size of 100 patients may have been insufficient to detect a modest HbA1c difference. The trial was only 24 weeks long. The high rate of GI side effects (58% nausea) may have affected adherence and could limit real-world applicability. The study was funded by Novo Nordisk, liraglutide's manufacturer. Only overweight patients with poor control were included, limiting generalizability.
How to read the evidence
This is a well-designed randomized, double-blind, placebo-controlled trial published in The Lancet Diabetes & Endocrinology. It provides strong evidence, though the primary endpoint was not met and the sample size was relatively small.
When this study was published
Published in 2016, this was one of the first RCTs testing a GLP-1 agonist in type 1 diabetes. The findings remain relevant as newer GLP-1 drugs are being tested in this population.
The bigger picture
GLP-1 agonists are not approved for type 1 diabetes, but off-label use is growing among overweight patients who need help with weight and insulin requirements. This trial — one of the first rigorous RCTs in this space — shows the benefits are real but the primary goal of better blood sugar control was missed. Later studies with semaglutide and tirzepatide in type 1 diabetes have continued exploring this question.
Questions still open
- Would a longer trial or higher-potency GLP-1 agonist like semaglutide show significant HbA1c improvement in type 1 diabetes?
- Is the 6.8 kg weight loss alone sufficient reason to prescribe GLP-1 agonists off-label in overweight type 1 diabetes patients?
- Could the 18% reduction in hypoglycemic events translate to improved quality of life and safety in real-world practice?
Common questions
Can people with type 1 diabetes use GLP-1 drugs like liraglutide?
Why didn't liraglutide improve blood sugar in type 1 diabetes if it works in type 2?
Read the original research
Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1): a randomised, double-blind, placebo-controlled trial.
The lancet. Diabetes & endocrinology, 4(3), 221-232
Citation
Dejgaard, Thomas Fremming; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk; Almdal, Thomas; Urhammer, Søren; Pedersen-Bjergaard, Ulrik; Jensen, Tonny; Jensen, Andreas Kryger; Holst, Jens Juul; Tarnow, Lise; Knop, Filip Krag; Madsbad, Sten; Andersen, Henrik Ullits. (2016). Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1): a randomised, double-blind, placebo-controlled trial.. The lancet. Diabetes & endocrinology, 4(3), 221-232. https://doi.org/10.1016/S2213-8587(15)00436-2