Neobook — clinical reference

MECHANISM OF ACTION

Acarbose is an oligosaccaride that competitively inhibits alpha glucosidase on the brush border of the small intestine.This inhibits the conversion of complex carbohydrates into monosaccharides, and results in a reduction and delay in the absorption of glucose. The nett effect is a decrease in post prandial plasma glucose.

EFFICACY ^1,2

In a meta-analysis of 30 randomised controlled trials, Acarbose monotherapy reduced HbA1C by 0.8% without causing hypoglycaemia or weight gain. The dose of 100 mg three times daily was not more effective than addition to metformin, sulphonylurea and insulin, which resulted in HbA1C reductions of 0.8%, 0.9% and 0.5%, respectively. In all studies, Acarbose significantly reduced postprandial glucose (2.3-3.5 mmol/l), and caused statistically significant weight loss or was weight neutral.

The Gluco VIP³ observational study of 15,034 patients showed a mean two hour PPG decreased by 4 mmol/l and a mean HbA1C reduction of 1.1%.

CARDIOVASCULAR EFFECTS

The Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM)⁴ trial randomly assigned 1 429 patients with impaired glucose tolerance to Acarbose 100 mg three times daily or placebo for a mean of 3.3 years. In a pre-planned secondary analysis, Acarbose significantly reduced the risk of cardiovascular events by 49%, and the risk of developing hypertension was decreased by 34%. The magnitude of the effect is unexpected and may be related to the fact that Acarbose targets postprandial hyperglycaemia (an independent risk factor for cardiovascular disease), but it needs verification. However, positive cardiovascular outcomes trials have been difficult to achieve, and these results should not be ignored.

ACE (Acarbose Cardiovascular Evaluation) Trial⁵ is a four year, multi-centre, double-blind, randomised parallel-group trial to determine whether reducing post-prandial glycaemia with Acarbose can reduce cardiovascular-related morbidity in patients with established coronary heart disease or acute coronary syndrome who have impaired glucose tolerance. Primary Outcome is occurrence of any of the following; Cardiovascular death, Non-fatal MI, Non-fatal stroke [Time Frame: 7500 patients followed-up for approximately four years until 904 adjudicated Primary Outcome Measures have been recorded]. Trial is due to report results in 2018.

DOSING

Start with 50 mg once daily with meals, and increase by 50 mg every two weeks if tolerated. The maximum dose is 100 mg three times daily, although a meta-analysis showed the same glycaemic benefit and better tolerability with 50 mg three times daily. Not recommended for use in eGFR <30 ml/min.

ADVERSE EFFECTS

At higher doses, Acarbose may give rise to transient elevation of hepatic transaminases. Patients up titrated to maximum dose should be closely monitored for the first 6 months. If elevated transaminases are observed a reduction in dosage is warranted. If elevated transaminase levels persist, then withdrawal of therapy may be warranted. Acarbose does not cause hypoglycaemia when used as monotherapy, but may aggravate hypoglycaemia caused by sulphonylureas and insulin.Gastrointestinal side-effects (flatulence and diarrhoea)Are common when initiating therapy, and are related to fermentation of the high saccharide load in the colon. This has led to discontinuation rates as high as 35% in clinical trials.

Side- effects can be minimised by slow dose titration. During the Gluco VIP Study³ conducted in 15 countries/regions in which 15,661 patients were considered valid for safety analysis, drug tolerability was rated as 'very good' or 'good' in 84.9 % of patients. Drug-related adverse events, mainly gastrointestinal, were reported in 490/15 661 patients (3.13 %). The investigators concluded that Acarbose is safe and well tolerated in a large cohort of Asian patients with type 2 diabetes.

PREGNANCY

Safety and Efficacy has not been established – Category B.

Author: Zaheer Bayat

References

Van de Laar FA, Lucassen PL, Akkermans RP, et al. Alpha-glucosidase inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev(2). 2005:CD003639.
Chiasson JL, Josse RG, Hunt JA, et al. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial. Ann Intern Med. 1994;121(12):928.
Chiasson JL, Josse RG, Gomis R, et al. STOP-NIDDM Trial Research Group. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA. 2003;290(4):486.
Acarbose Cardiovascular Evaluation Trail. https://www.dtu.ox.ac.uk/ace/. Accessed 24th February 2016
Zhang W, Kim D, Philip E, et al. A multinational, observational study to investigate the efficacy, safety and tolerability of acarbose as add-on or monotherapy in a range of patients: the Gluco VIP study. Clin Drug Investig. 2013: 33(4):263-74.