Type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a chronic progressive metabolic disease and is reaching epidemic proportions in China. In adults 18 years and older in China, the prevalence of diabetes was 11.6%, with a total number of 113.9 million in 2010; China has become the country with the largest diabetic population. T2DM accounts for at least 90% of all cases of diabetes. This disease has brought a great burden in terms of health care costs and socioeconomic consequences. Glycosylated hemoglobin (HbA1c) is the gold standard that reflects the glycemic control level, and Chinese Diabetes Society's (CDS) and American Diabetes Association's (ADA) guidelines are taking HbA1c < 7.0% as the glycemic control goal criteria. However, the Chinese goal-achieving rate is poor; approximately only 39.7% of diabetics are with adequate glycemic control in 2010[1].

Since T2DM is mainly the result of insulin resistance, currently approved medications for the treatment of Type-2 diabetes focus on reducing insulin resistance and preventing weight gain by different mechanisms of action. Acarbose (Alpha-Glucosidase Inhibitor) and metformin are T2DM medications. Acarbose inhibits digestion into monosaccharides and offsetting post-prandial glucose rise while metformin inhibits hepatic glucose production and improves peripheral insulin sensitivity.

Metformin

Metformin is an inexpensive glucose-lowering agent offering proven efficacy and safety. As a selective hepatic insulin-sensitizing drug, It can reduce HbA1c by 1.0%- 1.5% by improving insulin sensitivity and decreasing intestinal absorption of glucose. It can either keep weight stability or reduce weight modestly for T2DM patients. Moreover, metformin has demonstrated long-term effectiveness and safety as a medication for diabetes prevention. In addition to the glucose-lowering effect, metformin also reduces fat accumulation, improves dyslipidemia, and lowers the levels of inflammatory and prothrombotic markers. Consistent with these metabolic benefits, randomized clinical trials demonstrated that diabetic patients receiving metformin treatment are less likely to develop macrovascular complications than those receiving conventional therapy (primarily diet) or placebo. Metformin also showed greater effects than sulfonylurea/insulin for any diabetes-related mortality, all-cause mortality, and stroke. Based on these favourable evidence, metformin is currently recommended as first-line therapy for type 2 diabetes by several international guidelines[2].

Acarbose

Acarbose is an α-glucosidase inhibitor that delays carbohydrate absorption in the intestines and is commonly used as monotherapy for mild diabetes or in combination with other therapies for more advanced diabetes. Previous randomized clinical trials demonstrated that acarbose is as effective as metformin for glycemic control. Furthermore, in the STOP-NIDDM study, acarbose treatment was shown to prevent 49% of cardiovascular events in patients with impaired glucose tolerance (IGT). Acarbose also slows the progression of carotid intima-media thickness in IGT patients. In a meta-analysis pooling 7 placebo-controlled clinical trials, acarbose treatment in type 2 diabetic patients reduces the risk of myocardial infarction (MI) by 64% and the risk of any cardiovascular event by 35%. These data suggest acarbose might be an alternative first-line oral therapy for type 2 diabetes with possible cardio-protective effects comparable to metformin. Therefore, acarbose has been recommending recently by international guidelines as an alternative first-line antidiabetic therapy, especially in the Asian population[3].

The glucose-lowering effect

In order to observe the differences between metformin and acarbose in glucose-lowering effect more intuitively, an indirect treatment comparison (ITC) of metformin with acarbose was conducted using a placebo as the common comparator. The results showed statistically significant differences that metformin reduced HbA1c levels by 0.38% more than acarbose (WMD, -0.38%, 95%CI, -0.736% to -0.024%). Thus, the indirect comparison suggested that the glucose-lowering effect of metformin was superior to that of acarbose.

Researchers performed an ITC of metformin with acarbose by using sulphonylureas as the common comparator, which revealed that metformin achieved a statistically greater reduction of 0.34% in HbA1c levels compared to acarbose (WMD, -0.34%, 95%CI, -0.651% to -0.029%). Thus, the glucose-lowering effect of metformin was superior to that of acarbose.

Due to the differences in mechanism and site of action between metformin and acarbose, there may be differences in the effects of glucose lowering. However, in the use of oral hypoglycemic agents in China, both metformin (53.7%) and α-glucosidase inhibitors (including acarbose, 35.9%) are commonly accepted and widely used either as monotherapy or in combination with other oral agents or insulin for the treatment of T2DM.

References

[1] Shuyan Gu. “Comparison of glucose lowering effect of metformin and acarbose in type 2 diabetes mellitus: a meta-analysis.” PLoS ONE (2015): e0126704.

[2] Chia-Hsuin Chang. “Cardiovascular risk associated with acarbose versus metformin as the first-line treatment in patients with type 2 diabetes: a nationwide cohort study.” Journal of Clinical Endocrinology &Metabolism (2015): 1121–9.

[3] Amir Ziaee, Maryam Honardoost, Neda Esmailzadehha. “Comparison of adjunctive therapy with metformin and acarbose in patients with Type-1 diabetes mellitus.” Pakistan Journal of Medical Sciences 33 3 (2017): 686–690.