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Acarbose: an alternative to metformin for first-line treatment in type 2 diabetes?

Acarbose: an alternative to metformin for fi rst-line
treatment in type 2 diabetes?

Most guidelines currently recommend metformin as and acarbose showed a signifi cant rise in GLP-1 Published Online
the fi rst-line treatment for type 2 diabetes1–3 on the basis
concentrations from 24 weeks onwards, although October 18, 2013 of data mostly generated in European populations. the decreases in glucagon seen in both groups S2213-8587(13)70107-4
Asia represents the region with the largest number were apparent mainly from 24 weeks onwards and See Online/Articles
of patients with diabetes worldwide, with more occurred earlier with acarbose than with metformin. S2213-8587(13)70021-4than 90 million in China alone.4 Asians with type 2 Further studies to investigate these changes would diabetes can have several characteristics in terms of be of interest. The increase in GLP-1 concentrations pathophysiology and pattern of complications that after acarbose is a marker of delayed and more distal might therefore need a slightly diff erent approach to intestinal absorption of carbohydrate.8 treatment.5,6 Nevertheless, large-scale randomised Gastrointestinal adverse eff ects were reported in 27% controlled trials in diff erent ethnic groups are scarce, and of patients receiving acarbose and 29% of those receiving most current national or regional treatment guidelines metformin. The low incidence of gastrointestinal are largely based on those of the USA or Europe.
intolerance seen in the acarbose group could be partly In The Lancet Diabetes & Endocrinology, Wenying Yang related to the “start low, go slow” approach adopted, with and colleagues7 report the fi ndings of a randomised gradual weekly titration from 50 mg a day during the fi rst controlled trial that compared the α-glucosidase week to 100 mg three times a week over a 4-week period. inhibitor acarbose with metformin as initial treatment The authors concluded that although metformin should for type 2 diabetes. Investigators in the MARCH still be considered the fi rst-line treatment, in patients (Metformin and AcaRbose in Chinese as the initial with a marked postprandial glucose excursion or with a Hypoglycaemic treatment) trial recruited 788 Chinese body-mass index similar to those recruited in the current patients aged 30–70 years who were newly diagnosed study, acarbose would be a worthy alternative.
with type 2 diabetes.7 Patients were randomly assigned α-glucosidase inhibitors remain most popular in to receive metformin (up to 1500 mg sustained release countries such as China and Japan, where rice forms preparation) or acarbose (titrated gradually up to a a major component of the diet and the dietary maximum of 100 mg three times a day). At the end contribution of carbohydrate is high. In the MARCH of the 48-week study period, acarbose was found to study, the mean contribution of carbohydrates for be non-inferior to metformin in terms of its HbA - energy intake was more than 65%, which was higher lowering eff ect (least-squares mean diff erence 0·01% than what was recommended in international guidelines [95% CI –0·12 to 0·14; p=0·8999]), and both treat ment (45–65%) and guidelines in China (up to 65%). The regimens achieved weight loss, although patients in the acarbose group lost slightly more weight (–0·63 kg [–1·15 to –0·10; p=0·0194]). Patients assigned to the acarbose group also had a more favourable lipid profi le, with improved HDL and lower triglycerides at 48 weeks. As expected, treatment with acarbose was associated with less postprandial hyperinsulinaemia than with metformin. Of particular note is the detailed characterisation of changes in gastrointestional hormones during treatment. Although both treatments show similar patterns of changes in glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucagon levels, there were also important diff erences (fi gure). Both metformin Figure: Mechanisms of action of acarbose
www.thelancet.com/diabetes-endocrinology Published online October 18, 2013 http://dx.doi.org/10.1016/S2213-8587(13)70107-4
results of this large study indicate that the effi cacy of eff ect of acarbose will be addressed in the Acarbose acarbose could be related to the carbohydrate content Cardiovascular Evaluation (ACE) Trial (NCT00829660, in the patients’ diet, which suggests that acarbose ISRCTN91899513), which is examining the cardio-would be more eff ective in populations with a high vascular outcome in patients with established carbohydrate intake. In a recent meta-analysis of 46 cardiovascular disease or acute coronary syndrome who studies,9 the glucose-lowering eff ects of acarbose did also have impaired glucose tolerance. seem greater in patients with type 2 diabetes consuming The MARCH trial has provided invaluable information an eastern Asian diet than in those on a western diet about the effi cacy and benefi ts of acarbose compared (including patients in Europe and North America). The with metformin. MARCH represents an applaudable mean HbA reduction in studies from eastern Asia was contribution and important step towards the signifi cantly lower at 1·54% (SD 2·0%) compared with development of evidence-based and population-specifi c 0·52% (1·2%) in studies of patients on a western diet.9 treatment guidelines for type 2 diabetes.
Whether this diff erence in effi the higher carbohydrate content in eastern diets is not Ronald CW Maclear. Another study has suggested that Asian patients Department of Medicine and Therapeutics, Prince of Wales had greater glycaemic responses to the same foods Hospital; The Li Ka Shing Institute of Health Sciences; and Hong Kong Institute of Diabetes and Obesity, Chinese University of than did white patients.10 Other potential factors that Hong Kong, Hong Kong Special Administrative Region, China could contribute to the diff erence in effi populations include underlying genetic factors and the I have received speaker honoraria or consultancy fees from Boehringer-composition of the gut microbiome.
Ingelheim, Eli Lilly, Bayer, Danone, Nestle, Pfi zer, and Takeda, and research support for clinical studies and trials from Astra Zeneca and Merck Sharp and With the advent of newer agents including GLP-1 Dohme. All proceeds have been donated to the Chinese University of Hong Kong receptor agonists and dipeptidyl peptidase-4 (DPP4) to support diabetes research.
inhibitors, α-glucosidase inhibitors might have moved 1 Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the down in the list of preferred choices of glucose-lowering American Diabetes Association (ADA) and the European Association for
the Study of Diabetes (EASD). Diabetologia 2012; 55: 1577–96.
treatment. Nevertheless, there is also the increasing 2 The International Diabetes Federation. Global guidelines for type 2 appreciation that the choice of treatment agents, as diabetes. Brussels: International Diabetes Federation, 2012: 57.
Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE comprehensive diabetes well as glycaemic targets, should be individualised management algorithm 2013. Endocr Pract 2013; 19: 327–36.
on the basis of patient characteristics.1 In the recent 4 Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China. N Engl J Med 2010; 362: 1090–101.
glycaemic control algorithm developed by the American 5 Ma RC, Chan JC. Type 2 diabetes in East Asians: similarities and diff erences Association of Clinical Endocrinologists, newer agents with populations in Europe and the United States. Ann N Y Acad Sci 2013;
1281: 64–91.
including DPP4 inhibitors, GLP-1 receptor agonists, 6 Kong AP, Xu G, Brown N, So WY, Ma RC, Chan JC. Diabetes and its and α-glucosidase inhibitors have been proposed as comorbidities-where East meets West. Nat Rev Endocrinol 2013; 9: 537–47.
Yang W, Liu J, Shan Z, et al. Acarbose compared with metformin as initial alternative fi rst-line treatments to metformin.3 therapy in patients with newly diagnosed type 2 diabetes: Although these important results from the MARCH an open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol 2013; published online Oct 18. http://dx.doi.org/10.1016/S2213- study provide evidence to support acarbose as a useful Qualmann C, Nauck MA, Holst JJ, Orskov C, Creutzfeldt W. Glucagon-like alternative to metformin as fi rst-line treatment, peptide 1 (7-36 amide) secretion in response to luminal sucrose from the there are currently little medium-term data for the upper and lower gut. A study using alpha-glucosidase inhibition
(acarbose). Scand J Gastroenterol 1995; 30: 892–96.
other agents being compared with metformin as 9 Zhu Q, Tong Y, Wu T, Li J, Tong N. Comparison of the hypoglycemic eff ect of monotherapy. Additional data for the medium-term acarbose monotherapy in patients with type 2 diabetes mellitus consuming an eastern or western diet: a systematic meta-analysis. Clin Ther and long-term outcome of patients receiving these 2013; 35: 880–99.
10 Henry CJ, Lightowler HJ, Newens K, et al. Glycaemic index of common foods newer agents compared with metformin are eagerly tested in the UK and India. Br J Nutr 2008; 99: 840–45.
awaited. Metformin has been linked with benefi cial cardiovascular outcomes, as well as decreased risk of cancer in type 2 diabetes. The long-term cardiovascular www.thelancet.com/diabetes-endocrinology Published online October 18, 2013 http://dx.doi.org/10.1016/S2213-8587(13)70107-4

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