According to the amlodipine package insert, hyperglycemia occurs in <1% but >0.1% of patients.1 Several studies further illustrate that calcium channel blockers (CCBs) have a negligible effect on blood sugar.2-8
In the ALLHAT trial 33,357 participants were randomized to receive chlorthalidone, amlodipine, or lisinopril as a first line agent for the treatment of hypertension.2 The incidence of new onset diabetes at four years in the chlorthalidone, amlodipine and lisinopril groups were 11.6%, 9.8%, and 8.1%, respectively. In the amlodipine group mean fasting glucose remained relatively unchanged throughout the study (123.1 mg/dL at baseline, 122.4 mg/dL at two years and 123.7 mg/dL at four years). A sub-study of the VALUE trials evaluated the effects of valsartan and amlodipine on preventing type 2 diabetes.3 Throughout the study (average follow-up of 4.2 years) mean glucose levels among the 4,963 participants randomized to the amlodipine group remained unchanged (p < 0.0001).
Ferrari et al. studied the effects of amlodipine in 38 healthy male volunteers (non-diabetic and non-hypertensive).4 After a one week placebo run-phase, participants were given amlodipine 5 mg for three weeks. Mean fasting plasma insulin and glucose levels, as well as insulin sensitivity did not differ significantly between the placebo and amlodipine phases.
Baggio et al. conducted a six week study of type 2 diabetics with hypertension.5 Participants were randomized to receive either felodipine 10 mg (n=16), amlodipine 10 mg (n=17), or placebo (n=20). In both the felodipine and amlodipine group, there was no significant changes in glucose tolerance, C-peptide secretion, fructosamine levels, and hemoglobin A1c levels.
Padwal et al. studied the incidence of type 2 diabetes among new users of antihypertensives.6 The study included 100,653 non-diabetic patients 66 years of age and older with a mean follow-up of 9.5 months who were newly prescribed monotherapy with either ACE inhibitors, calcium channel blockers, thiazide diuretics or β-blockers. Calcium channel blockers did not increase the risk of developing diabetes.
Studies have compared the effects of amlodipine to those of other antihypertensives with regard to blood sugar levels. In a study that compared nifedipine to co-amilozide, (hydrochlorothiazide/amiloride), diabetes occurred in 4.3% of nifedipine users compared to 5.6% of co-amilozide users (p=0.02).7 Participants aged 55-80 were included in the study if they had a blood pressure (BP) ≥150/95 mm Hg or a systolic BP ≥160 mm Hg, and had at least one additional cardiovascular risk factor. The rate of the primary endpoint (cardiovascular death, myocardial infarction, heart failure, or stroke) in diabetics was 8.3% in the nifedipine group and 8.4% in the co-amilozide group.
A randomized, double-blind, study paralleled the effects of amlodipine and enalapril on glucose metabolism and insulin sensitivity in non-diabetic patients with mild to moderate hypertension.8 Mild to moderate hypertension was defined as a sitting diastolic BP between 95 and 114 mm Hg. In the amlodipine group insulin mediated glucose uptake increased from 3.63 ± 0.32 to 3.97 ± 0.31 mg/kg/min (p=0.02). Insulin sensitivity also increased from 1.15 ± 0.11 to 1.39 ± in the amlodipine group (p=0.03). In the enalapril group insulin mediated glucose uptake and insulin sensitivity increased from 3.59 ± 0.32 to 3.94 ± 0.3 mg/kg/min (p=0.09) and from 1.25 ± 0.13 to 1.49 ± 0.16 (p=0.01), respectively.
The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends the use of diuretics, β-blockers, ACE inhibitors, or calcium channel blockers in diabetic hypertensives.9 The European Society of Hypertension and the European Society of Cardiology (ESH/ESC) practice guidelines state that all effective and well tolerated antihypertensives can be used in patients with diabetes, including calcium antagonists.10 For patients at high risk of incident diabetes, the ESH/ESC does not recommend the use of β-blockers, especially in combination with thiazide diuretics. These recommendations suggest that calcium channel blockers are safe to use in diabetics because they do not cause a significant increase in blood glucose.
References
- Amlodipine. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda
- Group ACR. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Jama. 2002;288(23):2981-2997.
- Kjeldsen SE, Julius S, Mancia G, et al. Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients: the VALUE trial. Journal of Hypertension. 2006;24(7):1405-1412.
- Ferrari P, Giachino D, Weidmann P, et al. Unaltered insulin sensitivity during calcium channel blockade with amlodipine. European Journal of Clinical Pharmacology. 1991;41(2):109-113.
- Baggio E, Maraffi F, Montalto C, et al. The effects of felodipine and amlodipine on glucose and lipid metabolism in patients affected by non—insulin-dependent diabetes mellitus and hypertension: a comparative, randomized, parallel-group study. Current therapeutic research. 1995;56(10):1050-1058.
- Padwal R, Mamdani M, Alter DA, et al. Antihypertensive Therapy and Incidence of Type 2 Diabetes in an Elderly Cohort. Diabetes Care. 2004;27(10):2458-2463.
- Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). The Lancet. 2000/07/29/ 2000;356(9227):366-372.
- Lender D, Arauz-Pacheco C, Breen L, Mora-Mora P, Ramirez LC, Raskin P. A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients. American journal of hypertension. 1999;12(3):298-303.
- Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. Jama. 2003;289(19):2560-2571.
- Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertensionThe Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). European Heart Journal. 2013;34(28):2159-2219.
