Non-Insulin Drugs for Type 1 Diabetes: A Review of What Works and What Doesn't | Research

The takeaway

A review found that non-insulin drugs including GLP-1 agonists and pramlintide provide only modest HbA1c improvements (0.2-0.5%) when added to insulin therapy in type 1 diabetes.

0.2–0.5% HbA1c reduction
The average improvement across all non-insulin adjunct drug classes — a modest benefit that highlights the limitations of repurposing type 2 diabetes drugs for type 1

What the researchers found

This review evaluated all non-insulin drugs studied as add-on therapies for type 1 diabetes, including pramlintide (an amylin analog), GLP-1 receptor agonists, DPP-4 inhibitors, SGLT1/SGLT2 inhibitors, metformin, sulfonylureas, and thiazolidinediones. The bottom line: none provided dramatic improvement. Average HbA1c reductions were a modest 0.2-0.5% (2-6 mmol/mol) across all drug classes.

At the time of publication, SGLT inhibitors were considered the most promising avenue for further development in type 1 diabetes. The authors identified obese type 1 patients, those with residual beta-cell function, and hypoglycemia-prone patients as subgroups most likely to benefit from adjunct therapy.

Why it matters

Many people with type 1 diabetes struggle to achieve blood sugar targets even with intensive insulin therapy. The success of peptide-based drugs like GLP-1 agonists and pramlintide in type 2 diabetes raised hopes they could help type 1 patients too. This review provides a realistic assessment: the benefits exist but are modest, highlighting the fundamental difference between type 1 (autoimmune destruction of insulin-producing cells) and type 2 diabetes.

The numbers in context

HbA1c reduction: 0.2-0.5% average · 7 drug classes reviewed · Pramlintide, GLP-1 RAs, DPP-4 inhibitors, SGLT1/2 inhibitors, metformin, sulfonylureas, thiazolidinediones

How the study worked

Expert review of published clinical trial evidence on non-insulin pharmacological therapies used as adjuncts to insulin in type 1 diabetes, covering efficacy, safety, and adverse event profiles across seven drug classes.

Who was studied

Review of clinical trials in type 1 diabetes patients receiving non-insulin adjunct therapies

What this study cannot tell us

Published in 2018, so it predates more recent data on GLP-1 agonists in type 1 diabetes and the FDA's partial approval/rejection of SGLT2 inhibitors for this indication. The modest benefits observed may partly reflect the challenge of studying add-on therapies when baseline insulin therapy already addresses the primary deficiency.

How to read the evidence

This is an expert review published in Expert Opinion on Pharmacotherapy that synthesizes clinical trial evidence across multiple drug classes. The quality of underlying evidence varies but includes randomized controlled trials for most drug classes discussed.

When this study was published

Published in 2018, this review captures the state of knowledge before more recent GLP-1 agonist data in type 1 diabetes. The landscape has continued to evolve, particularly regarding SGLT2 inhibitors and newer GLP-1 drugs.

The bigger picture

The modest results highlight a fundamental challenge: type 1 diabetes isn't primarily a problem of insufficient GLP-1 or amylin signaling — it's an autoimmune destruction of beta cells. While peptide adjuncts like pramlintide (which replaces the missing amylin hormone) have logical mechanisms, the disease biology limits how much additional benefit they can provide on top of insulin. This review helps set realistic expectations for peptide therapies in type 1 diabetes.

Questions still open

Could newer GLP-1 agonists like semaglutide or tirzepatide provide larger benefits in type 1 diabetes than the older agents reviewed here?
Are there specific type 1 diabetes subpopulations (obese, newly diagnosed, residual beta-cell function) where peptide adjuncts provide clinically meaningful benefits?
Could combining multiple adjunct therapies (e.g., GLP-1 agonist + SGLT2 inhibitor + insulin) achieve better results than single add-on approaches?

Common questions

Can people with type 1 diabetes take Ozempic or other GLP-1 drugs?

GLP-1 receptor agonists are not FDA-approved for type 1 diabetes, but some doctors prescribe them off-label, particularly for type 1 patients who also struggle with weight. This review found they provide modest HbA1c improvements of about 0.2-0.5% when added to insulin. They may be most useful for overweight type 1 patients who need help with blood sugar control and weight management.

Why don't type 2 diabetes drugs work as well in type 1?

Type 1 diabetes is caused by autoimmune destruction of insulin-producing beta cells, while type 2 is primarily an insulin resistance problem. Drugs like GLP-1 agonists partly work by helping remaining beta cells produce more insulin — but type 1 patients have few or no functioning beta cells left. So these drugs can provide some incremental benefits (like slowing stomach emptying and reducing glucagon), but they can't address the core problem.

Read the original research

Non-insulin pharmacological therapies for treating type 1 diabetes.

Expert opinion on pharmacotherapy, 19(9), 947-960

View on PubMed ↗Publisher’s paper ↗

Citation

Frandsen, Christian Seerup; Dejgaard, Thomas Fremming; Madsbad, Sten; Holst, Jens Juul. (2018). Non-insulin pharmacological therapies for treating type 1 diabetes.. Expert opinion on pharmacotherapy, 19(9), 947-960. https://doi.org/10.1080/14656566.2018.1483339