Related Experiment Video
Updated: Jan 6, 2026
A High-Throughput Multiplexed Screening for Type 1 Diabetes, Celiac Diseases, and COVID-19
Published on: July 5, 2022
SGLT2 inhibitors as adjunctive therapy for type 1 diabetes: balancing benefits and risks
Simeon I Taylor1, Jenny E Blau2, Kristina I Rother3
1Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Sodium-glucose co-transporter-2 (SGLT2) inhibitors have several beneficial effects in patients with type 2 diabetes, including glucose lowering, weight loss, blood pressure lowering, and a reduced risk of major adverse cardiovascular events. To address high unmet medical need via improved glycaemic control, several clinical trials have been done to assess the efficacy and safety of SGLT2 inhibitors in combination with insulin therapy in patients with type 1 diabetes. In this Personal View, we summarise data from eight clinical trials of canagliflozin, dapagliflozin, empagliflozin, and sotagliflozin in patients with type 1 diabetes. HbA1c-lowering efficacy was greatest at 8-12 weeks of therapy, but the magnitude of HbA1c lowering waned with longer duration of treatment (up to 52 weeks). Data are not yet available to establish for how long glycaemic efficacy could be sustained during long-term therapy in patients with type 1 diabetes. Moreover, SGLT2 inhibitor therapy induces serious adverse events, including a roughly six-times increased risk of diabetic ketoacidosis. The US Food and Drug Administration estimated that one additional case of ketoacidosis will occur for every 26 patient-years of exposure of patients with type 1 diabetes to sotagliflozin therapy. Assuming a case mortality of 0·4%, this estimate translates into 16 additional deaths per year per 100 000 patients with type 1 diabetes undergoing treatment. These considerations raise important questions about the risk-to-benefit profile of SGLT2 inhibitors when used as adjunctive therapy in patients with type 1 diabetes.
Insights
Sodium-glucose co-transporter-2 (SGLT2) inhibitors show initial benefits for type 1 diabetes but pose risks. Their efficacy wanes over time, and they significantly increase the risk of diabetic ketoacidosis, questioning their overall benefit.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Pharmacology
Background:
- Sodium-glucose co-transporter-2 (SGLT2) inhibitors are established treatments for type 2 diabetes, offering glucose lowering, weight loss, and cardiovascular benefits.
- Unmet needs in type 1 diabetes management include improved glycemic control and reduced complication risks.
- SGLT2 inhibitors are being investigated as adjunctive therapy in type 1 diabetes to enhance glycemic control.
Purpose of the Study:
- To summarize the efficacy and safety data of SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, sotagliflozin) as add-on therapy in patients with type 1 diabetes.
- To evaluate the glycemic efficacy, including HbA1c reduction, and safety profile of SGLT2 inhibitors in this population.
- To assess the risk-benefit profile of SGLT2 inhibitors in type 1 diabetes, considering adverse events like diabetic ketoacidosis.
Main Methods:
- Systematic review and summary of data from eight clinical trials involving SGLT2 inhibitors in patients with type 1 diabetes.
- Analysis of glycemic efficacy, specifically HbA1c reduction over time (up to 52 weeks).
- Assessment of safety data, focusing on the incidence and risk of serious adverse events, particularly diabetic ketoacidosis.
Main Results:
- SGLT2 inhibitors demonstrated greatest HbA1c-lowering efficacy at 8-12 weeks of therapy.
- The magnitude of HbA1c reduction waned with longer treatment durations (up to 52 weeks).
- SGLT2 inhibitor therapy was associated with a significantly increased risk of diabetic ketoacidosis (DKA), estimated at a six-fold increase, raising concerns about patient safety.
Conclusions:
- While SGLT2 inhibitors show initial glycemic benefits in type 1 diabetes, their efficacy diminishes over time.
- The substantial increase in the risk of diabetic ketoacidosis is a major safety concern for SGLT2 inhibitor use in type 1 diabetes.
- The risk-benefit profile of SGLT2 inhibitors as adjunctive therapy in type 1 diabetes requires careful consideration due to safety risks, particularly DKA.
Related Concept Videos
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:23Dipeptidyl Peptidase 4 Inhibitors
01:06Oral Hypoglycemic Agents: Glinides
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:17Oral Hypoglycemic Agents: Sulfonylureas
01:22Diabetes Mellitus: Type 2 and Gestational