Combining GLP-1 Drugs with Pramlintide for Weight Loss in Type 1 Diabetes: Three Patient Cases | Research

The takeaway

Three patients with type 1 diabetes and obesity lost 14-23% of their body weight using a GLP-1 drug combined with pramlintide, with no significant side effects and stable or improved blood sugar.

Up to 23.1% body weight lost
One patient lost nearly a quarter of her body weight over 7 months on dulaglutide plus pramlintide, with total weight loss of 21.2 kg

What the researchers found

Three patients with type 1 diabetes and obesity achieved substantial weight loss using a combination of a GLP-1 receptor agonist and pramlintide (an amylin analog). Patient 1 lost 20.9 kg (16.1% of body weight) over 10 months on semaglutide plus pramlintide. Patient 2 lost a total of 21.2 kg (23.1% of body weight) after adding dulaglutide and pramlintide to her regimen. Patient 3 lost 14.6 kg (17.9% of body weight) over 6 months on semaglutide plus pramlintide. All three experienced no significant side effects, needed less insulin, and maintained or improved their HbA1c levels.

Why it matters

People with type 1 diabetes who also have obesity face a unique challenge: most weight loss drugs are studied in type 2 diabetes patients, leaving a significant treatment gap. This case series suggests that combining a GLP-1 drug with pramlintide may produce impressive weight loss in this underserved population without worsening blood sugar control — potentially by targeting appetite through two complementary gut-brain pathways.

How the study worked

This is a case series describing three patients seen in clinical practice. Each patient with type 1 diabetes and obesity was prescribed a GLP-1 receptor agonist (semaglutide or dulaglutide) in combination with pramlintide. Weight, HbA1c, insulin requirements, and side effects were tracked over 6 to 10 months of treatment.

Who was studied

Three adults with type 1 diabetes and obesity (ages 32-68), with various comorbidities

What this study cannot tell us

As a case series of only 3 patients, this provides the lowest level of clinical evidence. There was no control group, no randomization, and no blinding. Individual results may not be generalizable. The follow-up period was relatively short (6-10 months), so long-term efficacy and safety are unknown. One patient was also on topiramate, making it harder to attribute all weight loss to the peptide combination.

How to read the evidence

Rated Low because this is a case series of only 3 patients with no control group or randomization. While the results are striking, case reports represent the lowest tier of clinical evidence and cannot establish causation.

When this study was published

Published in 2023, this case series reflects current clinical practice and is relevant to the growing interest in GLP-1 drugs for type 1 diabetes, though larger studies are needed.

The bigger picture

The GLP-1 drug revolution has primarily focused on type 2 diabetes and general obesity. People with type 1 diabetes have largely been left out of these advances. This case series hints that combining GLP-1 agonism with amylin replacement — two natural gut-brain signaling pathways — could fill that gap. If confirmed in larger studies, it would open a new treatment avenue for a population that currently has few pharmacological options for weight management.

Questions still open

Would a randomized controlled trial confirm the synergistic weight loss effect of combining GLP-1 agonists with pramlintide in type 1 diabetes?
Could this combination increase the risk of hypoglycemia over longer treatment periods as insulin doses are reduced?
What is the optimal dosing strategy for combining these two peptide classes in type 1 diabetes?

Common questions

Why combine a GLP-1 drug with pramlintide instead of using one alone?

GLP-1 drugs and pramlintide work through different but complementary pathways in the gut-brain axis. GLP-1 agonists mimic the incretin hormone GLP-1, while pramlintide mimics amylin, a hormone co-secreted with insulin. Together, they may produce greater appetite suppression and weight loss than either alone, which these three cases seem to support.

Are GLP-1 drugs approved for use in type 1 diabetes?

GLP-1 receptor agonists are not FDA-approved for type 1 diabetes — they're approved for type 2 diabetes and/or obesity. Using them in type 1 diabetes patients is considered off-label. Pramlintide, however, is approved for both type 1 and type 2 diabetes.

Read the original research

Combined GLP-1 Receptor Agonist and Amylin Analogue Pharmacotherapy to Treat Obesity Comorbid With Type 1 Diabetes.

JCEM case reports, 1(2), luad040

View on PubMed ↗Publisher’s paper ↗

Citation

Wong, Gunther; Garner, Erica M; Srivastava, Gitanjali. (2023). Combined GLP-1 Receptor Agonist and Amylin Analogue Pharmacotherapy to Treat Obesity Comorbid With Type 1 Diabetes.. JCEM case reports, 1(2), luad040. https://doi.org/10.1210/jcemcr/luad040