Canagliflozin for Those on Triple Drug Therapy with Uncontrolled Diabetes 

SGLT-2 inhibitors, such as canagliflozin, have proved to be successful hypoglycemics, so should they be recommended earlier for those not achieving goal A1c reductions? 

Studies have proved sodium-glucose cotransporter 2 (SGLT-2) inhibitors to be useful glucose and A1c lowering therapy in a broad range of patients with type 2 diabetes. Recent studies have assessed their effects on type 1 diabetes, and other studies have concluded that SGLT-2 inhibitors reduce cardiovascular events in people with type 2 diabetes. SGLT-2 inhibitors have been recommended as second-line therapies for those whose safety profiles correlate to the medication. Insulin is used when HbA1c levels are extremely high or when are person is in a state of severe hyperglycemia. Many people are titrated up to insulin once oral therapies have failed. In many instances, patients are reluctant to begin insulin therapy because of its route of administration, a side effect of weight gain, and risk of hypoglycemia. In this analysis, changes in HbA1c and weight are being evaluated for patients who were unwilling to take insulin and received canagliflozin after inadequate responses to maximum doses of 3 oral hypoglycemic agents.  

This trial was a 12-week, open-label, single-center, single-arm, interventional study done at Deogiri Diabetes Center, Aurangabad. In this study, 118 patients aged 18 to 65 years old, received canagliflozin 100 mg once daily in addition to an ongoing triple-drug, oral hypoglycemic agents’ regimen. Seventy-six participants were male, and 42 were female. Inclusion criteria were type 2 diabetes patients on a maximum of 3 oral hypoglycemic agents, HbA1c >8.5%, and BMI >25. Newly diagnosed people with type 2 diabetes, type 1 diabetes mellitus, gestational diabetes, patients with eGFR values less than 45 ml/min, patients on insulin therapy, patients with recurrent UTI and patients with a history of diabetic ketoacidosis or other co-morbid cardiac, hepatic and renal diseases were excluded. The primary endpoint was change in HbA1c from baseline up to 12 weeks. The secondary endpoint was change in body weight from baseline up to 12 weeks. A paired t-test was used to analyze the data. 

Out of 118 participants, four withdrew. The reasons for withdrawal were three adverse drug reactions and one drop out. The adverse drug reaction, urinary tract infection, occurred only in women. The results of the study presented at week 12 concluded that canagliflozin 100 mg provided significant reductions in HbA1c from baseline (p<0.001). The mean change in A1c was -1.94%, and more significant reductions were seen in the higher baseline A1c patients. Notable weight reductions were also observed. The mean difference in weight loss was -3.01 kg (p<0.001). The most significant change was seen within the first six weeks.  

Canagliflozin proved to be a useful add on therapy for those on max doses of 3 oral hypoglycemic agents. This study is unique because it is the first to try canagliflozin as an add on treatment to patients on three max dose oral medications. The population was small and not diverse, and the follow-up period was short as well. Therefore, more studies need to be conducted to properly access canagliflozin’s place as an add on to triple-drug therapy. With positive effects such as reductions in weight and HbA1c and low risks of hypoglycemia, SGLT-2 inhibitors are becoming recognized as a top choice of treatment for people with type 2 diabetes. 

Practice Pearls: 

• Canagliflozin is effective in reducing weight and HbA1c levels.
• Patients with high risk or history of urinary tract infections should avoid SGLT-2 inhibitors.
• More research is needed for quadruple oral hypoglycemic therapy.

Bhosle D, Quazi Z, Chavan S, Shaikh H. Efficacy and Safety of Canagliflozin in Patients with Type II Diabetes Mellitus Inadequately Controlled on Triple Drug Therapy. J Assoc Physicians India. 2019 Oct;67(10):36-38. 

Antonio Bess, PharmD. Candidate, Florida Agricultural & Mechanical University School of Pharmacy