Antimalarial drug effective alternative to canagliflozin in type 2 diabetes
LOS ANGELES — Adults with type 2 diabetes inadequately controlled with a DPP-IV inhibitor plus metformin therapy experienced an improvement in glycemic control with the antimalarial drug hydroxychloroquine that was similar to the SGLT2 inhibitor canagliflozin, according to study data presented here.
In a randomized, parallel-group, open-label study comparing the safety and efficacy of hydroxychloroquine vs. canagliflozin (Invokana, Janssen), researchers also found that patients assigned to hydroxychloroquine experienced a greater reduction in BMI and high-sensitivity C-reactive protein when compared with the canagliflozin group.
“Hydroxychloroquine, the same treatment we know as an antimalarial drug, the same treatment we know as an antirheumatic drug, now has a completely new relevance,” Amit Gupta, MD, an endocrinologist at the GD Diabetes Institute in Kolkata, West Bengal, India, said during a presentation at the AACE Annual Scientific and Clinical Congress. “We’ve known this drug has some effect on glycemic parameters since the 1950s, but what really made a difference was in 2014, when the Drug Controller General of India approved this drug as an add-on drug for those diabetic patients who failed two oral antihyperglycemic agents, which is quite a common scenario.”
Gupta and colleagues analyzed data from 87 patients with type 2 diabetes with no history of cardiovascular or renal events already prescribed 100 mg vildagliptin plus 2,000 mg daily metformin therapy (66.2% men; mean age, 56 years; mean BMI, 27.6 kg/m²; mean diabetes duration, 6.1 years). Patients were randomly assigned to 400 mg hydroxychloroquine (n = 43) or 300 mg canagliflozin (n = 44) for 24 weeks. Primary outcome was change from baseline in HbA1c at 24 weeks. Additional analyses included changes in fasting plasma glucose, postprandial glucose and body weight, as well as adverse events including hypoglycemia.
At 24 weeks, patients in both groups experienced a similar reduction in HbA1c; however, the between-group difference did not rise to significance (P = .029). Mean HbA1c fell from a mean of 8.32% to 7.11% in the hydroxychloroquine group (P = .001) and from 8.6% to 7.44% in the canagliflozin group (P = .001).
During the study, mean FPG levels decreased from 143 mg/dL to 112 mg/dL in the hydroxychloroquine group (P = .001) and from 147 mg/dL to 117 mg/dL in the canagliflozin group (P = .001). Similarly, postprandial glucose decreased in both groups over 24 weeks, from a mean of 210 mg/dL to 142 mg/dL in the hydroxychloroquine group (P = .001) and from 219 mg/dL to 153 mg/dL in the canagliflozin group (P = .001).
Gupta noted that mean BMI remained stable during the study for the canagliflozin group (P = .312), but decreased in the hydroxychloroquine group, from a mean of 27.2 kg/m² to 25.69 kg/m² (P = .003). Additionally, patients in the hydroxychloroquine group reported less hypoglycemia vs. patients in the canagliflozin group (5.4% vs. 8.2%) and experienced fewer confirmed hypoglycemic events (0 vs. 2.27%), Gupta said.
Most interesting to the researchers, Gupta said, was a greater reduction in high-sensitivity C-reactive protein in the hydroxychloroquine group vs. the canagliflozin group, which decreased from a mean of 2.8 mg/L to 1.9 mg/L in the hydroxychloroquine group (P = .001) and from a mean of 2.7 mg/L to 2.5 mg/L in the canagliflozin group (P = .38).
“In [India], where cost is a major factor, people who cannot afford a costly drug like canagliflozin ... can use hydroxychloroquine as an alternative, which is shown to be quite safe and efficacious,” Gupta said. “Hydroxychloroquine, with its dual properties of reducing blood sugar and as an anti-inflammatory drug, can emerge as an important drug in the arsenal of antidiabetic regimens.” – by Regina Schaffer
Gupta A, et al. A real-world observational comparative study for the efficacy and tolerability of hydroxychloroquine vs. canagliflozin in Indian type 2 diabetes patients having inadequate glycemic control on vildagliptin plus metformin. Presented at: AACE Annual Scientific and Clinical Congress; April 24-28, 2019; Los Angeles.
Disclosure: Gupta reports no relevant financial disclosures.