Assistant Professor, Department of Medicine, D. Y Patil Medical Collage, Kasaba Bawda, Kolhapur, D Y Patil Medical Collage And Hospital, Kadamwadi, Kolhapur, Maharashtra, INDIA.

Email: dr.buddhirajpatil86@gmail.com

RESULTS

Baseline data of both study group patients is shown in table 1. Mean age was comparable in both groups. Female patients were more in both groups. Other high-risk factors such as hypertension, smoking, dyslipidaemia, coronary artery disease, chronic obstructive pulmonary disease were present in both groups. In diabetes mellites group 58% patients had less than 5 years duration of diabetes.

Table 1: Baseline data of patients

We analysed HbA1c, fasting blood sugar and postprandial blood sugar values from both groups. A significant difference was noted in HbA1c values in diabetes group. In normal glucose tolerance difference was not significant.

Table 2: Analysis of HbA1c

*(Statistical tests considered significant if P-value is <0.05)

In diabetes group, we noted a significant difference in fasting blood sugar values taken at 6 months follow up compared to values at start of study. Small reduction in fasting blood sugar values noted at 6 months follow up in normal glucose tolerance as compared to values at start of study, difference was not significant.

Table 3: Analysis of fasting blood sugar (FBS)

*(Statistical tests considered significant if P-value is <0.05)

A significant difference in postprandial blood sugar values noted in diabetes group, while in normal glucose tolerance difference was not significant.

Table 4: Analysis of postprandial blood sugar (PBS)

*(Statistical tests considered significant if P-value is <0.05)

DISCUSSION

Basic management of type 2 diabetes mellitus (T2DM) consists of lifestyle measures (diet and exercise), oral antidiabetic drugs, and if required then insulin. Drug Controller General of India (DCGI) approved Hydroxychloroquine (HCQ) as add-on therapy in Type 2 Diabetes (T2DM) patients inadequately controlled despite lifestyle management along with sulfonylurea and metformin combination therapy.⁹ Research Society for the Study of Diabetes in India (RSSDI) in clinical practice recommendations 2017, recommended hydroxychloroquine (HCQ) as add-on therapy in Type 2 Diabetes patients. ⁹ In a randomized, placebo-controlled trial in nondiabetic patients with stable RA, Solomon et al. noted that treatment with HCQ had no significant change in insulin sensitivity index and insulin resistance compared to placebo, but a significant reduction in total cholesterol and LDL-cholesterol was noted.¹⁰ In present study we noticed insignificant difference in HbA1c, fasting blood sugar and postprandial blood sugar values of non-diabetic patients. Other studies demonstrated that HCQ use is associated with a significantly reduced risk of developing diabetes in nondiabetic subjects with inflammatory rheumatic diseases, such as rheumatoid arthritis, SLE, Sjogren syndrome and psoriasis.^11-13 Gupta A. noted in study with poorly controlled type 2 diabetes patients not willing to start insulin, noted that hydroxychloroquine (400 mg/d) is associated with marked reductions in fasting plasma glucose, hemoglobin A1c and body weight.⁶ Similar findings were noted in Indian randomized controlled trial.¹⁴ In present study we noted significant reduction in HbA1c, fasting blood sugar and postprandial blood sugar values in diabetic patients at end of 6 month HCQ treatment.  In a review evaluating the effect of hydroxychloroquine on indices of glycemic control and/or cardiovascular events in people with Type 2 Diabetes, they noted abundant evidence for metabolic benefit of HCQ.¹⁵ In a clinical study in nondiabetic, obese individuals, it was noted that HCQ improved b-cell function, insulin sensitivity and adiponectin levels significantly as compared to placebo.⁵  Though in present study hypoglycemia was not reported by any patient during study period, but case reports are present for hypoglycemia due to hydroxychloroquine in diabetic and non-diabetic patients.^16-18 For patients receiving chloroquine or hydroxychloroquine, physicians should warn patients about the possibility of hypoglycemia and describe its manifestations.¹⁹ Management of hypoglycemia involves cessation of the drug and administration of supplemental glucose or parenteral dextrose if needed. Clinical data on long-term safety and efficacy of HCQ in diabetes are still lacking. HCQ use in patients with diabetes should be carefully evaluated. Common complications due to long term HCQ use are retinal toxicity. HCQ-mediated cardiotoxic effects (heart rhythm disorders, such as prolonged QT interval, ventricular arrhythmia, and Torsade’s de Pointes), particularly in high-risk subjects.²⁰ In chronic kidney diseases, HCQ clearance can be reduced, causing increased drug bioavailability and subsequent augmented risk of HCQ related side effects. ²⁰ Whole world is facing coronavirus disease-2019 (COVID-19) pandemic, which is one of the important event in the recent history of mankind, declared a global pandemic by the World Health Organization on 11 March 2020. A Chinese study, showed that chloroquine and HCQ inhibit SARSCoV-2 in vitro with HCQ and found it to be more potent than chloroquine. So, HCQ was recommended for treatment of COVID 19 patients. A proper risk-benefit assessment of HCQ use in diabetic patients should also be considered in relation to the current coronavirus disease 2019 (COVID-19) pandemic.²² In diabetic patients who are already on HCQ for treatment of diabetes, the effect of HCQ on glycemia, cardiovascular function and viral load needs to be researched. Limitations of present study were short duration of treatment and small sample size. Prospective multicentric clinical trials with longer follow-up of subjects are required to confirm the results of the present study.

CONCLUSION

Hydroxychloroquine decreases HbA1c, fasting blood sugar and postprandial blood sugar values in patients with type 2 diabetes. Considering the anti-hyperglycemic potential, anti-inflammatory activity HCQ can considered as a therapeutic option for uncontrolled diabetes patients. A careful risk-benefit assessment is required for cautious use of HCQ in subjects with diabetes.

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