GLP-1 Drugs vs SGLT2 Inhibitors in Type 1 Diabetes: Real-World Heart and Kidney Outcomes | Research

The takeaway

In a real-world study of nearly 200,000 type 1 diabetes patients, SGLT2 inhibitors preserved kidney function and reduced heart failure risk compared to GLP-1 receptor agonists, but carried higher rates of diabetic ketoacidosis.

56% lower heart failure risk
Type 1 diabetes patients on SGLT2 inhibitors were 56% less likely to develop heart failure over 5 years compared to those on GLP-1 receptor agonists

What the researchers found

Among 196,691 type 1 diabetes patients, 1,822 were treated with GLP-1 RAs and 992 with SGLT2 inhibitors for at least 6 months. Both lowered HbA1c: SGLT2i reduced it by 2.6 mmol/mol (0.2%) and GLP-1 RA by 5.4 mmol/mol (0.5%).

Over 5 years, SGLT2i users showed kidney function preservation (eGFR +3.5 ml/min/1.73m²) while GLP-1 RA users showed decline (eGFR -7.2 ml/min/1.73m²). SGLT2i users had significantly lower risks of heart failure (RR 0.44, p=0.009), chronic kidney disease (RR 0.49, p=0.012), and all-cause hospitalization (RR 0.59, p<0.0001). However, SGLT2i users had higher rates of diabetic ketoacidosis (RR 2.08, p=0.031) and urinary tract infections (RR 2.27, p=0.019).

Why it matters

Type 1 diabetes patients face high rates of kidney disease and heart failure over their lifetimes, and insulin alone doesn't fully protect against these complications. This is the largest real-world study comparing GLP-1 RAs and SGLT2 inhibitors in type 1 diabetes, providing crucial evidence for an off-label use that many clinicians are already prescribing. The stark difference in kidney outcomes could influence treatment decisions for thousands of patients.

How the study worked

This was a retrospective cohort study using the TriNetX platform, a global network of anonymized real-time medical records. Researchers identified all adults with type 1 diabetes who had been treated with either SGLT2 inhibitors or GLP-1 RAs for at least 6 months alongside insulin. They analyzed HbA1c changes, kidney function (eGFR), adverse events, and cardio-renal outcomes over a 5-year follow-up period.

What this study cannot tell us

This is a retrospective observational study, so it cannot prove causation. The TriNetX platform may have coding inaccuracies, and some patients may have been misclassified between type 1 and type 2 diabetes. The SGLT2i group was smaller (992 vs 1,822) and there may be selection bias in which patients received each drug. Propensity score matching details were not described in the abstract. The higher DKA risk with SGLT2i is a known class effect that may be manageable with proper patient education.

How to read the evidence

This is a large retrospective real-world cohort study using electronic health records. While the sample size is substantial and outcomes are clinically meaningful, the observational design means confounding factors may influence results. It represents stronger evidence than clinical trials for this off-label indication, since randomized trials in type 1 diabetes are limited.

When this study was published

Published in 2023, this study provides current real-world evidence on a pressing clinical question. The off-label use of both drug classes in type 1 diabetes continues to evolve as more data becomes available.

The bigger picture

GLP-1 receptor agonists have become blockbuster drugs primarily for type 2 diabetes and obesity, but their role in type 1 diabetes is less clear. This study suggests that while GLP-1 RAs provide better blood sugar control in type 1 diabetes, SGLT2 inhibitors may be the better choice for long-term organ protection. The findings add to a growing recognition that type 1 diabetes management should extend beyond glucose control to include cardiovascular and renal risk reduction — and that different drug classes offer different protective profiles.

Questions still open

Could combining SGLT2 inhibitors and GLP-1 RAs in type 1 diabetes provide both the glucose-lowering benefits and the organ-protective effects?
Why did GLP-1 RAs show a decline in kidney function over 5 years, given their renoprotective effects in type 2 diabetes?
Can the elevated DKA risk with SGLT2 inhibitors in type 1 diabetes be mitigated with better patient monitoring protocols?

Common questions

Why are GLP-1 drugs and SGLT2 inhibitors used off-label in type 1 diabetes?

Both drug classes are approved for type 2 diabetes, but some type 1 diabetes patients struggle to maintain good blood sugar control with insulin alone. These adjunctive therapies can help lower blood sugar, reduce insulin doses, and potentially protect against heart and kidney complications. However, they are not officially approved for type 1 diabetes, so their use requires careful clinical judgment.

What is diabetic ketoacidosis and why is it a concern with SGLT2 inhibitors?

Diabetic ketoacidosis (DKA) is a dangerous condition where the body produces excess ketones, making the blood acidic. In type 1 diabetes patients, SGLT2 inhibitors can trigger DKA even when blood sugar levels appear normal (called euglycemic DKA), making it harder to detect. This study found SGLT2i users had double the DKA risk compared to GLP-1 RA users, emphasizing the need for careful monitoring.

Read the original research

SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study.

Diabetologia, 66(10), 1869-1881

View on PubMed ↗Publisher’s paper ↗

Citation

Anson, Matthew; Zhao, Sizheng S; Austin, Philip; Ibarburu, Gema H; Malik, Rayaz A; Alam, Uazman. (2023). SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study.. Diabetologia, 66(10), 1869-1881. https://doi.org/10.1007/s00125-023-05975-8