Efficacy and safety of canagliflozin, an inhibitor of sodium-glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes
Abstract
Objective There are limited data about the effects of sodium-glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin. Research design and methods The CANagliflozin CardioVascular Assessment Study is a double-blind, placebo-controlled study that randomized participants to placebo, canagliflozin 100 mg, or canagliflozin 300 mg once daily, added to a range of therapies. The primary end point of this substudy was the change in HbA1c from baseline at 18 weeks among patients using insulin; 52-week effects were also examined. Results Individuals receiving insulin at baseline were randomized to receive placebo (n = 690), canagliflozin 100 mg (n = 692), or canagliflozin 300 mg (n = 690). These individuals were 66% male and had a median age of 63 years, mean HbA1c of 8.3% (67 mmol/mol), BMI of 33.1 kg/m(2), estimated glomerular filtration rate of 75 mL/min/1.73 m(2), fasting plasma glucose of 9.2 mmol/L, and a median daily insulin dose of 60 IU. Most individuals were using basal/bolus insulin. Reductions in HbA1c with canagliflozin 100 and 300 mg versus placebo were -0.62% (95% CI -0.69, -0.54; -6.8 mmol/mol [95% CI -7.5, -5.9]; P Conclusions Canagliflozin added to insulin therapy improved glycemic control and decreased body weight. There was a greater frequency of several anticipated side effects, although few led to discontinuation of treatment.
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The risk of hypoglycemia is low with SGLT2i monotherapy, as the drug-induced glycosuria decreases as blood glucose normalizes, but the risk may be increased when this therapy is used concomitantly with other medications that can cause hypoglycemia, such as sulfonylureas or insulin.
“The risk of hypoglycemia is low with SGLT2i monotherapy, as the drug-induced glycosuria decreases as blood glucose normalizes, but the risk may be increased when this therapy is used concomitantly with other medications that can cause hypoglycemia, such as sulfonylureas or insulin.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [150]
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- Authors
- Neal, B., Perkovic, V., de Zeeuw, D., Mahaffey, K. W., Fulcher, G., Ways, K., Desai, M., Shaw, W., Capuano, G., Alba, M., Jiang, J., Vercruysse, F., Meininger, G., Matthews, D., & on behalf of the CANVAS Trial Collaborative Group
- Affiliations
- The University of Sydney (AU)
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
- Stanford Medicine (US)
- Janssen Research & Development (United States) (US)
- University of Oxford (GB)
- Corresponding author
- Neal, Bruce
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2014-12-02
- Volume
- 38
- Issue
- 3
- Pages
- 403-411
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2141800817
- Cited by
- 233
- References
- 1
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 13 · 2022: 13 · 2021: 9 · 2020: 11 · 2019: 22 · 2018: 25 · 2017: 36 · 2016: 49 · 2015: 31
- FWCI
- 31.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- GlaxoSmithKline
- Servier
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- canagliflozin, SGLT2 inhibitors, type 2 diabetes, insulin therapy, multiple daily insulin injections, HbA1c, glycemic control, drug safety, combination therapy, cardiovascular outcomes, renal outcomes, hypoglycemia, diabetic ketoacidosis, urinary tract infection
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Blood Glucose, Blood Pressure, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Glomerular Filtration Rate, Glucosides, Glycosuria, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Middle Aged, Mycoses, Thiophenes, Urinary Tract Infections, Weight Loss, Treatment Outcome, Hypovolemia
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