Canagliflozin and Amputation Risk: Evidence So Far
Eleni Papadokostaki1, Evangelos Rizos2,3, Stelios Tigas3
1General Hospital of Heraklion Venizeleio-Pananeio, Heraklion, Greece.
The International Journal of Lower Extremity Wounds
|November 9, 2019
Summary
Sodium-glucose cotransporter 2 inhibitors (SGLT2i), particularly canagliflozin, show a controversial risk for lower limb amputation. Further evidence is needed, but caution is advised for high-risk patients.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Nephrology
Background:
- Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are used to manage type 2 diabetes.
- The CANVAS program suggested an increased risk of lower limb amputation with canagliflozin.
Purpose of the Study:
- To evaluate the association between SGLT2 inhibitors and the risk of lower limb amputation.
- To clarify whether amputation risk is specific to canagliflozin or a class effect of SGLT2 inhibitors.
Main Methods:
- Review of clinical trial data (CANVAS, CREDENCE) and other observational studies.
- Analysis of randomized controlled trials involving dapagliflozin and empagliflozin.
Main Results:
- Canagliflozin showed a 2-fold increased risk of amputation in the CANVAS program, but not confirmed in CREDENCE.
- Other SGLT2 inhibitors (dapagliflozin, empagliflozin) did not demonstrate increased amputation risk in RCTs.
- Observational studies and pharmacovigilance reports yielded conflicting results regarding SGLT2i and amputation.
Conclusions:
- The link between SGLT2 inhibitors and lower limb amputation remains controversial.
- It is unclear if the risk is a canagliflozin-specific effect or a broader SGLT2i class effect.
- Clinicians should exercise caution with SGLT2i, especially canagliflozin, in patients with a history of amputation or foot ulceration.
Related Concept Videos
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
547
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
547
01:22Diabetes Mellitus: Type 2 and Gestational
4.2K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
4.2K
01:23Dipeptidyl Peptidase 4 Inhibitors
525
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
525
01:15Diabetes: Symptoms, Diagnosis, and Complications
2.0K
For most patients, experiencing several weeks of polyuria, polydipsia, fatigue, and significant weight loss may indicate the presence of diabetes. Furthermore, adults displaying the phenotypic appearance of type 2 diabetes (particularly those who are obese and not initially insulin-requiring), may have islet cell autoantibodies, suggesting autoimmune-mediated β cell destruction and a diagnosis of latent autoimmune diabetes of adults (LADA). The categorization of glucose homeostasis is...
2.0K
01:06Oral Hypoglycemic Agents: Glinides
542
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
542
01:20Pathophysiology of Diabetes
3.0K
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
3.0K