Could an Anti-Malarial be Adjunctive T2D Therapy?

LOS ANGELES — Hydroxychloroquine (HCQ, Plaquenil) might be a candidate as adjunctive therapy in type 2 diabetes, researchers reported here.

Among adults patients with uncontrolled type 2 diabetes already on vildagliptin (Galvus, Zomelis) and metformin, HCQ significantly reduced HbA1c compared with baseline after 24 weeks (8.32% vs 7.11%, P =0.001), according to Amit Gupta, MD, of the G.D. Diabetes Institute in Kolkata, India, and colleagues.

The reduction in HbA1c was analogous to that of adding the SGLT-2 inhibitor canagliflozin (Invokana) as adjunctive therapy (8.63% vs 7.44%, P =0.001), they reported at the American Association of Clinical Endocrinologists (AACE) annual meeting.

After 24 weeks of therapy, the reduction in A1c among patients who added HCQ versus canagliflozin was not significantly different, Gupta said.

HCQ, most often used to treat malaria, was approved as an adjunctive type 2 diabetes in India in 2014. The efficacy of the drug as an add-on therapy for diabetes "already exists in the literature and was nothing new," Gupta explained to MedPage Today . With the current study, he and his colleagues wanted to determine "whether it translated the same way from a research setting to a real-world scenario, which in fact happened," he added.

"HCQ is an anti inflammatory drug, which can address residual risk beyond glycemic control, so don’t hesitate to include it as an option," Gupta recommended, also underscoring that "inflammation is the [connection] between diabetes and cardiovascular [CV] mortality."

Hydroxychloroquine is currently FDA-approved for the treatment of malaria, lupus, and rheumatoid arthritis.

The National Institute of Diabetes and Digestive and Kidney Diseases is recruiting patients for a trial of hydroxychloroquine in individuals at-risk for type 1 diabetes (estimated study completion date August 2024). Other U.S. studies are looking at metabolic effects of hydroxychloroquine and using hydroxychloroquine in pre-diabetes . A study of hydroxychloroquine versus pioglitazone (Actos) in combination treatment for type 2 diabetes was terminated early.

The current observational, open-label study included 87 Indian patients with type 2 diabetes (age around 56; 58% male) who were already treated with a maximum dose of 100 mg of the DPP-4 inhibitor vildagliptin and 2,000 mg of metformin daily. None of the patients had a history of CV events or retinal abnormalities. Half of the patients were placed on 400 mg of HCQ once daily, while the other half of the cohort were placed on 300 mg of canagliflozin once daily.

After 24 weeks of adjunctive treatment, fasting plasma glucose (FPG) and postprandial glucose levels (PPG) significantly dropped in both the HCQ group and the canagliflozin group, with no significant differences in this decrease between the two medications: FPG in HCQ: 143 mg/dL vs 112 mg/dL

FPG in canagliflozin: 147 mg/dL vs 117 mg/dL

PPG in HCQ: 210 mg/dL vs 142 mg/dL

PPG in canagliflozin: 219 mg/dL vs 153 mg/dL

BMI significantly dropped in patients on HCQ — from 27.2 to 25.69 — but there wasn’t a significant change for those on canagliflozin (27.9 vs 27). Similarly, only high-sensitivity C-reactive protein levels dropped significantly in the HCQ group (2.8 mg/L vs 1.9 mg/L) but not in the canagliflozin group (2.7 mg/L vs 2.5 mg/L).

Rates of hypoglycemia were also slightly lowered among patients on HCQ versus canagliflozin (5.4% vs 8.2%). Similar rates were reported for confirmed cases of hypoglycemia throughout the study, defined as symptoms of hypoglycemia paired with a glucose reading less than 50 mg/dL (0% for HCQ vs 2.27% for canagliflozin).

The main takeaway from these findings is that HCQ is "an effective and safe medication in diabetics so it can be used as cheaper add-on drug to failing oral agents or insulin," Gupta explained. He added that the cost of HCQ runs about one-tenth of the cost of canagliflozin in India.

"I don’t think most people in this country know anything about HCQ for this use, and cost is a big thing here, too," commented AACE session moderator Lance Sloan, MD, of the Texas Institute for Kidney and Endocrine Disorders in Lufkin.

However, one benefit of canagliflozin that can’t be overlooked is the established benefit on CV prevention in type 2 diabetes, which was added to the agent’s labels in 2018. Gupta said his group is currently assessing CV outcomes with HCQ in an ongoing study, with expected results next year.

Gupta said he and his colleagues plan to continue follow the cohort in the current study for a longer period of time, and add patients to the cohort, to test durability of the glycemic control.

Gupta and co-authors disclosed no relevant relationships with industry.

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