Can canagliflozin improve insulin resistance and internal fat tissue in patients with type 2 diabetes better than metformin?

This study assessed the effects of canagliflozin (Invokana) therapy on body composition, glucose control, insulin resistance, and systemic (whole body) inflammation in patients with newly-diagnosed type 2 diabetes (T2D) compared to metformin (Glucophage). The data showed that canagliflozin therapy reduced visceral fat tissue, and improved blood glucose, insulin resistance, and systemic inflammation in these patients.

A main cause of T2D is insulin resistance. This means that the body cannot properly use insulin to lower blood glucose. The first drug commonly given to newly diagnosed patients with T2D is metformin, which improves insulin resistance. 

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) such as canagliflozin are oral glucose-lowering drugs used in the treatment of diabetes. SGLT2is may significantly reduce the risk of heart disease and chronic kidney failure in patients with diabetes. Insulin resistance and chronic inflammation have been linked to an increased waist circumference (abdominal obesity) in patients with T2D.

It is unknown whether improvements in insulin resistance and blood glucose levels with SGLTi treatments are related to decreased abdominal fat tissue. Dapagliflozin (Farxiga), a type of SGLT2i, has shown promising results in waist/hip ratio reductions, a marker for abdominal obesity, after 12 weeks of therapy. However, it is unclear whether this is due to reduced visceral fat tissue in patients with T2D and if these effects also extend to canagliflozin.

This study included 140 patients with newly-diagnosed T2D. Patients were assigned to 2 treatment groups. Group 1 included 67 patients who received 100 mg of canagliflozin once daily for 12 weeks. Group 2 included 73 patients who received 1000 mg of metformin, twice-daily for 12 weeks. Fat tissue images were obtained using abdominal cross-sections with computed tomography. Laboratory measurements and fasting insulin levels (mIU/mL) using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were determined.

After 12 weeks of treatment with canagliflozin, fasting blood glucose, HbA1c (blood glucose control over the past 2-3 months), and HOMA-IR were decreased, along with visceral (internal abdominal) fat tissue, compared to baseline measurements. Canagliflozin treatment resulted in lower fasting blood glucose, HbA1c, HOMA-IR, visceral fat tissue, and inflammatory blood markers compared to metformin treatment.

The study showed that canagliflozin therapy resulted in greater improvements in blood glucose control and insulin resistance and visceral fat reduction compared to metformin in patients with newly diagnosed T2D.

The study was done in a single center and was non-randomized. Researchers and patients were aware of the assigned treatment groups, potentially allowing bias to be introduced.