Adding Liraglutide to Insulin in Type 1 Diabetes: Benefits Real, But Safety Risks Limit Use
Liraglutide added to insulin in type 1 diabetes improved blood sugar and caused significant weight loss, but increased hypoglycemia and ketosis risk enough to limit its clinical usefulness.
Quick Facts
What This Study Found
Adding liraglutide to insulin therapy in type 1 diabetes modestly improved blood sugar control (HbA1c reduced 0.20% more than placebo at the 1.8 mg dose), reduced total insulin requirements by 8%, and produced significant weight loss (up to 4.9 kg at 1.8 mg vs placebo). However, these benefits came with increased rates of symptomatic hypoglycemia across all doses and a significantly higher rate of hyperglycemia with ketosis at the 1.8 mg dose (2.22× higher than placebo).
The safety trade-offs — more low blood sugar episodes and more ketosis events — were judged to limit the clinical usefulness of liraglutide in type 1 diabetes.
Key Numbers
n=1,398 · 52 weeks · HbA1c ETD: −0.20% (1.8 mg) · Insulin reduction: 8% (1.8 mg) · Weight loss: −4.9 kg (1.8 mg), −3.6 kg (1.2 mg), −2.2 kg (0.6 mg) · Hypoglycemia rate ratio: 1.31 (1.8 mg) · Ketosis rate ratio: 2.22 (1.8 mg only)
How They Did This
52-week, double-blind, randomized, placebo-controlled, treat-to-target trial. 1,398 adults with type 1 diabetes were randomized 3:1 to receive liraglutide (1.8, 1.2, or 0.6 mg) or placebo once daily via subcutaneous injection, added to their existing insulin regimen. Insulin doses were adjusted to maintain target blood glucose throughout the trial.
Why This Research Matters
This is the largest trial (ADJUNCT ONE) testing whether a GLP-1 agonist could benefit people with type 1 diabetes when added to insulin. While the metabolic benefits were real — better blood sugar, less insulin needed, weight loss — the increased risk of hypoglycemia and ketosis meant the drug wasn't safe enough for routine use in this population. This study is a key reason GLP-1 agonists remain off-label for type 1 diabetes.
The Bigger Picture
GLP-1 agonists have transformed treatment for type 2 diabetes and obesity, but their role in type 1 diabetes remains uncertain. ADJUNCT ONE is the definitive large trial showing why: the drugs deliver real metabolic benefits but introduce safety risks that are harder to manage when the body makes no insulin of its own. This hasn't stopped off-label use, but it explains why no GLP-1 agonist is approved for type 1 diabetes.
What This Study Doesn't Tell Us
The treat-to-target insulin adjustment protocol may have contributed to hypoglycemia by encouraging aggressive insulin dosing alongside liraglutide. The study population had mean baseline HbA1c of 8.2%, which may not represent all type 1 diabetes patients. The trial wasn't designed to identify which subgroups might benefit safely.
Questions This Raises
- ?Could newer GLP-1 agonists like semaglutide achieve the same benefits with fewer safety risks in type 1 diabetes?
- ?Are there specific subgroups of type 1 diabetes patients (e.g., those who are overweight) who could safely benefit from GLP-1 addition?
- ?Would different insulin adjustment protocols reduce the hypoglycemia risk when combining GLP-1 agonists with insulin?
Trust & Context
- Key Stat:
- −4.9 kg weight loss Liraglutide 1.8 mg added to insulin produced significant weight loss in type 1 diabetes, but hypoglycemia increased 31% and ketosis more than doubled
- Evidence Grade:
- This is a large (n=1,398), 52-week, double-blind, randomized, placebo-controlled trial published in Diabetes Care — one of the top diabetes journals. It represents high-quality evidence, though the post hoc nature of some analyses and the treat-to-target design introduce some limitations.
- Study Age:
- Published in 2016, ADJUNCT ONE remains the definitive large trial of liraglutide in type 1 diabetes. Its findings continue to inform clinical practice and explain why GLP-1 agonists remain off-label for this condition.
- Original Title:
- Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial.
- Published In:
- Diabetes care, 39(10), 1702-10 (2016)
- Authors:
- Mathieu, Chantal, Zinman, Bernard(2), Hemmingsson, Joanna Uddén, Woo, Vincent, Colman, Peter, Christiansen, Erik, Linder, Martin, Bode, Bruce
- Database ID:
- RPEP-03044
Evidence Hierarchy
Frequently Asked Questions
Can people with type 1 diabetes use GLP-1 drugs like liraglutide?
This trial showed that adding liraglutide to insulin improved blood sugar control and caused meaningful weight loss in type 1 diabetes. However, it also increased low blood sugar episodes and dangerous ketosis events, leading researchers to conclude the risks limit its clinical usefulness. GLP-1 drugs remain off-label for type 1 diabetes.
Why did liraglutide increase ketosis risk in type 1 diabetes?
When liraglutide reduces appetite and food intake while insulin doses are being lowered, the combination can create conditions favorable for ketone production — especially in people with type 1 diabetes who produce no insulin naturally. The 1.8 mg dose more than doubled the rate of hyperglycemia with ketosis, a potentially dangerous metabolic state.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-03044APA
Mathieu, Chantal; Zinman, Bernard; Hemmingsson, Joanna Uddén; Woo, Vincent; Colman, Peter; Christiansen, Erik; Linder, Martin; Bode, Bruce. (2016). Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial.. Diabetes care, 39(10), 1702-10. https://doi.org/10.2337/dc16-0691
MLA
Mathieu, Chantal, et al. "Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial.." Diabetes care, 2016. https://doi.org/10.2337/dc16-0691
RethinkPeptides
RethinkPeptides Research Database. "Efficacy and Safety of Liraglutide Added to Insulin Treatmen..." RPEP-03044. Retrieved from https://rethinkpeptides.com/research/mathieu-2016-efficacy-and-safety-of
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Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.