Acarbose therapy promotes vascular health
Acarbose is an α-glucosidase inhibitor prescribed for prevention and treatment of diabetes; it and metformin are the most commonly used diabetes drugs worldwide. Less than 2% of acarbose is absorbed after administration, rationalising its non-toxicity; its clinical utility evidently reflects its ability to slow absorption of dietary carbohydrate by acting within the intestinal tract to inhibit brush-border α-glucosidase, which plays a key role in the digestion of starch and sugars.1 ,2 Inhibition of α-glucosidase in saliva, and non-competitive inhibition of pancreatic α-amylase, also contribute to it slowing of carbohydrate absorption.3 Clinical doses of acarbose ingested with meals notably blunt the postprandial increase in serum glucose, a well-documented predictor of macrovascular and microvascular complications in diabetics, and of macrovascular risk in non-diabetics.4 ,5 A Cochrane meta-analysis found that, on average, acarbose therapy lowers glycated haemoglobin (HbA1c) levels by 0.8%, and reduces the postprandial increase in plasma glucose by 2.3 mM.6 Glycaemic control benefits of acarbose therapy tend to be greater in Asian clinical trials than in Western ones, likely because Asians tend to consume diets higher in carbohydrates.7 Gastrointestinal side effects of acarbose—reflecting carbohydrate malabsorption—are fairly common when initiating therapy, but tend to lessen over time as the distal intestine upregulates its capacity to absorb glucose. These side effects can be minimised by starting with a low dose—25 or 50 mg with two or three meals daily—and gradually raising it; in other words, ‘start low, go slow’.8 The maximal dose of acarbose is 100 mg three time a day—higher doses do not achieve a greater impact on carbohydrate digestion.
Like metformin, but unlike many other diabetes drugs, acarbose tends to promote weight loss, and cannot trigger hypoglycaemic episodes.9–11 Acarbose also resembles metformin in that there is reasonably compelling evidence that acarbose therapy in patients with diabetes or glucose intolerance has a favourable impact on cardiovascular health outcomes, and can slow the onset of diabetes in glucose-intolerant participants.2 ,12 ,13 Analyses of long-term outcomes in the Stop Non-insulin-dependent Diabetes Mellitus (STOP-NIDDM) trial, as well as a meta-analysis of longer-term controlled trials of acarbose in type 2 diabetics, conclude that risk for cardiovascular events, most notably myocardial infarction, is lower in acarbose-treated patients (HR=0.51; 95% CI 0.28 to 0.95 in STOP-NIDDM and HR=0.66; CI 0.48 to 0.88 in the diabetes treatment meta-analysis).14 ,15 A large multicenter controlled trial in China ongoing since 2009, the Acarbose Cardiovascular Evaluation study, should provide a more definitive determination of acarbose's capacity to promote vascular health.16
Acarbose therapy can favourably influence cardiovascular risk factors. In diabetics, acarbose therapy tends to lower mean blood pressure; in the STOP-NIDDM trial, incidence of newly diagnosed hypertension was 34% lower in the acarbose-treated group.14 ,17 Yet acarbose therapy also helps to prevent postprandial hypotension in elderly participants prone to this disorder.18 ,19 Serum triglyceride levels tend to drop, and high-density lipoprotein cholesterol to rise, during acarbose therapy.13 ,14 In early type 2 diabetes, acarbose therapy decreases urinary markers of platelet aggregation.20 Slowed progression of carotid intima-media thickness has also been reported in acarbose-treated patients, and acarbose therapy improves postprandial endothelium-dependent vasodilation.21–24 In rabbits subjected to 30 min of coronary occlusion followed by reperfusion, feeding acarbose for a week prior to the procedure was associated with a greater than 50% reduction in infarct size; this benefit was wholly abolished if an inhibitor of ATP-sensitive K channels (5-hydroxydecanoate) was administered slightly before onset of ischaemia.25