Impact of Bromocriptine-QR Therapy on Glycemic Control and Daily Insulin Requirement in Type 2 Diabetes Mellitus Subjects Whose Dysglycemia Is Poorly Controlled on High-Dose Insulin: A Pilot Study

Abstract

Background. The concurrent use of a postprandial insulin sensitizing agent, such as bromocriptine-QR, a quick release formulation of bromocriptine, a dopamine D2 receptor agonist, may offer a strategy to improve glycemic control and limit/reduce insulin requirement in type 2 diabetes (T2DM) patients on high-dose insulin. This open label pilot study evaluated this potential utility of bromocriptine-QR. Methods. Ten T2DM subjects on metformin (1-2 gm/day) and high-dose (TDID ≥ 65 U/day) basal-bolus insulin were enrolled to receive once daily (morning) bromocriptine-QR (1.6–4.8 mg/day) for 24 weeks. Subjects with at least one postbaseline HbA1c measurement (N = 8) were analyzed for change from baseline HbA1c, TDID, and postprandial glucose area under the curve of a four-hour mixed meal tolerance test (MMTT). Results. Compared to the baseline, average HbA1c decreased 1.76% (9.74 ± 0.56 to 7.98 ± 0.36, P = 0.01), average TDID decreased 27% (199 ± 33 to 147 ± 31, P = 0.009), and MMTT AUC60–240 decreased 32% (P = 0.04) over the treatment period. The decline in HbA1c and TDID was observed at 8 weeks and sustained over the remaining 16-week study duration. Conclusion. In this study, bromocriptine-QR therapy improved glycemic control and meal tolerance while reducing insulin requirement in T2DM subjects poorly controlled on high-dose insulin therapy.

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

“…Compared to the baseline, average HbA1c decreased 1.76% (9.74 ± 0.56-7.98 ± 0.36, P = 0.01), average total daily insulin requirement decreased 27% (from 199 ± 33 to 147 ± 31, P = 0.009) and MMTT area under the curve (AUC) decreased 32% (P = 0.04) over the 24-week bromocriptine-QR treatment period. The decline in HbA1c and total daily insulin requirement were observed at 8 weeks and sustained over the remaining 16-week study duration [179] (Figures 16 and 17). The more robust anti-hyperglycemic responses to bromocriptine-QR in T2DM subjects on insulin therapy versus those on SU therapy (−0.7 to −1.76 HbA1c reductions versus −0.6 to −0.83 HbA1c reductions, respectively) may reflect the better ability of exogenous insulin versus SU to raise the plasma insulin level that in turn interacts (additively or synergistically) with the insulin-sensitizing effects of bromocriptine-QR [163] to better improve glycemic control.…”

“…In the second open-label, single arm pilot study, 10 T2DM subjects on metformin (1-2 g/day) plus high dose basal-bolus insulin (minimum 65 U/day, subject population average daily dose = 190 U/day) were assigned treatment to bromocriptine-QR (1.6-4.8 mg/day, titrated up at a rate of 0.8 mg/week for a 6 weeks period to the maximum tolerated dose) for a 24 weeks period [179]. Changes from baseline in HbA1c, total daily insulin requirement, and area under the glucose curve from a 4 h mixed meal Figure 14.…”

“…As add-on therapy to TZD plus OAD, among subjects within the prespecified EPP analysis, bromocriptine-QR therapy for 52 weeks resulted in a −0.91 reduction in HbA1c versus placebo in T2DM subjects with baseline HbA1c of 8.3 [174]. In pilot studies, as add-on to insulin therapy, bromocriptine-QR treatment resulted in a −0.77 and −1.76 HbA1c reduction with concurrent insulin dose reductions of 8% and 25% in T2DM subjects with baseline HbA1c of 9.35 and 9.4, respectively [178,179]. Once-daily morning administration of bromocriptine-QR to T2DM subjects reduces postprandial hyperglycemia following each of the three meals of the day [162].…”

“…DPP4 Is, GLP-1 analogs, meglitinides, prandial insulin) to achieve complementary (additive or synergistic) effects on glycemic control (vis-à-vis insulin secretory stimulus plus insulin tissue response interactions) [133], though certain of these particular combination studies have yet to be conducted. In addition, results from pilot studies suggest that concurrent use of bromocriptine-QR in individuals with T2DM requiring moderateto-high doses of insulin may be an effective strategy to improve glycemic control while limiting insulin dose in these individuals [179]. Moreover, a substantive portion of the metabolic benefit from bromocriptine-QR therapy may be the result of its ability to reduce elevated sympathetic tone, a major potentiator of metabolic syndrome.…”

Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin

“…Available evidence from preclinical and clinical studies suggests that B-QR is a postprandial-weighted insulin sensitizer promoting glucose disposal following a meal [21][22][23][35][36][37][38][39]. Hyperinsulinemic-euglycemic clamp studies indicate that B-QR improves maximally insulin-stimulated glucose disposal [21].…”