While canagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), is known to reduce body weight and blood pressure (BP) in the short-term, a new study examined whether that effect persists over the longer term in patient with type 2 diabetes.

The study presented at the recent American Heart Association Scientific Sessions in Chicago also examined the relationship of drug dose and body weight.

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Reductions in body weight and better blood pressure control might be a factor in canagliflozin’s positive outcomes in reducing cardiovascular risk in type 2 diabetes mellitus (T2DM) patients, posited researchers from John H. Stroger Jr Hospital of Cook County, IL, and Northwestern University.

Their meta-analysis sought to study the effects of long term canagliflozin use on BP and body weight in those patients, stratifying the results by dosage.

The study team queried MEDLINE and Scopus in May 2018 for randomized controlled trials (RCTs) of canagliflozin that had a follow-up period of at least one year and reported change in BP and percentage change in body weight. They then pooled data from included studies, using a random effects model, with results presented as weighted mean differences (WMDs) with 95% confidence intervals (CIs).

At the same time, subgroup analysis was performed based on dosage from 100mg to 300 mg. Ultimately, 5 RCTs involving 15,230 participants) were included in the final analysis.

Results indicated that canagliflozin led to significant reduction in body weight when compared to controls (WMD: -3.32% [-4.04, -2.60]; P < 0.001), but the effect was not found to be dose-dependent (p=0.76).

Researchers reported that both systolic (WMD: -4.40 mmHg [-5.18, -3.62]; P < 0.001) and diastolic (WMD: -1.68 mmHg [-2.14, -1.23]; P < 0.001) BP were significantly lower with long-term canagliflozin use, when compared to placebo. In this case, the effect was found to be significantly stronger in the 300mg subgroup, when compared to the 100mg subgroup for both systolic (P=0.02) and diastolic (P=0.01) BP. No significant change in the risk of hypotension, however, was determined with the use of canagliflozin (Odds ratio: 1.59 [0.80, 3.19]; P=0.19). 

“Long-term canagliflozin is associated with reduced body weight and may be one mechanism for the beneficial BP response observed,” study authors concluded. “Favorable changes in body weight and BP may be responsible for improved cardiovascular outcomes in T2DM patients with canagliflozin.”