Acute glycaemic effects of co-trimoxazole at prophylactic dose in healthy adults

Cases of severe hypoglycaemia were reported in HIV/AIDS patients receiving high dose of the sulfonylurea co-trimoxazole for opportunistic infections. Whether co-trimoxazole at prophylactic dose would induce similar side effects is unknown. We aimed to investigate the acute effects of co-trimoxazole at prophylactic dose on glucose metabolism in healthy adults.

We enrolled 20 healthy volunteers (15 males and 5 females) aged 23.0 (SD 2.0) years, with mean BMI of 22.3 (SD 3.6) Kg/m² with normal glucose tolerance, hepatic and renal function. We performed a 75-g oral glucose tolerance test (OGTT) with and without concomitant oral co-trimoxazole administered 60 min before the test. Blood glucose response was measured using a capillary test at baseline and at 30, 60, 90, 120 and 180 min following oral glucose load on the two occasions. C-peptide response was also measured. Absolute values of blood glucose and C-peptide with and without co-trimoxazole were compared using the Wilcoxon test.

During the OGTT without co-trimoxazole (control) vs. the OGTT with co-trimoxazole (test), the glycaemia varied from 4.83 (SD 0.39) mmol/l vs. 4.72 (SD 0.28) mmol/l at T0 (P = 0.667), to 8.00 (SD 1.11) mmol/l vs. 7.44 (SD 0.78) mmol/l at T30 (P = 0.048), 8.00 (SD 1.17) mmol/l vs. 7.67 (SD 1.00) mmol/l at T60 (P = 0.121), 7.33 (SD 0.94) mmol/l vs. 7.11 (SD 0.83) mmol/l at T90 (P = 0.205), 6.78 (SD 1.00) mmol/l vs. 6.67 (SD 1.00) mmol/l at T120 (P = 0.351) and 4.72 (SD 1.39) mmol/l vs. 4.72 (SD 1.56) mmol/l at T180 (P = 0.747). The ratio of area under the glycaemia curve during the control and test investigation was 96.7 %, thus a 3.3 decreased glycaemic response (p = 0.062). A decrease of glycaemia by more than 10 % occurred in 6/20 participants at T30, 7/20 participants at T60 and 1/20 participant at T30 and T60. None of the volunteers experienced co-trimoxazole-induced hypoglycaemia. At the same time, the C-peptide response during the control vs. the test investigation varied from 278.1 (SD 57.5) pmol/l vs. 242.8 (SD 42.5) pmol/l at T0 (P = 0.138), to 1845.6 (SD 423.6) pmol/l vs. 2340.6 (SD 701.3) pmol/l at T60 (P = 0.345) and 1049.8 (SD 503.1) pmol/l vs. 1041.63 (SD 824.21) pmol/l at T180 (P = 0.893).

Ninety minutes after its administration, co-trimoxazole induced a significant reduction of the early glycaemic response to oral glucose in parallel with a 27-% increase in insulin secretory response. Co-trimoxazole induced within 120 min a more than 10-% blood glucose reduction in 2/3 of participants. However none of the volunteers experienced hypoglycaemia.