Metformin and Acupuncture in Overweight/Obese Patients with Type 2 Diabetes

Firouzjaei A, Li GC, Wang N, Liu WX, Zhu BM. Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients. Nutr Diabetes. 2016;6:e209. 

Randomized controlled trial (RCT) designed to compare the therapeutic effects of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity 

To compare the therapeutic effects of metformin as monotherapy with metformin combined with acupuncture on weight loss and insulin sensitivity in overweight/obese patients with type 2 diabetes mellitus

This RCT included 39 participants who were distributed by permuted-block randomization by an independent research assistant into a case group of 19 (8 men and 11 women) and a control group of 20 (8 men and 12 women). 

 

In order to be included in the study, participants had to be 20 to 65 years of age, overweight or obese [body mass index (BMI) ≥25 kg/m²], diagnosed with type 2 diabetes (according to diagnostic criteria for type 2 diabetes set by the American Diabetes Association), and on metformin monotherapy at doses of 500 mg 1, 2, or 3 times per day. 

 

Patients were excluded from the trial if they were already on insulin therapy for type 2 diabetes; had been on weight loss supplements, antidepressants, or hormonal medications within the past 3 months; or had any of the following conditions: nephrotic syndrome, edema, renal failure, heart failure or an implanted pacemaker, liver dysfunction as evidenced by aspartate aminotransferase (AST) and glutamate pyruvate transaminase levels two-fold above the normal range or a diagnosis of cirrhosis, glycohemoglobin level above 9%, endocrine disorders such as thyroid disease or polycystic ovary syndrome, disorders of homeostasis, or other systemic diseases. Pregnant and nursing mothers were also excluded.

In the case group, in addition to metformin, participants were treated with electroacupuncture with a frequency of 15 Hz/10 mA connected to 8 needles (ST25, SP15, ST28, REN 12; REN 6). Other body and ear acupoints were also included. All participants were treated 10 times, every other day, over a 3-week period. The control group was treated with “sham” acupuncture and metformin. 

The researchers compared body weight, BMI, inflammatory markers, lipid profiles, and adipokines in overweight/obese patients with type 2 diabetes receiving the combined therapy with those receiving metformin monotherapy.

Reductions in both body weight and BMI were seen in both groups. However, only the case group had significant differences in BMI (from 27.6±2.5 before treatment to 26.2±2.4 after treatment, P<0.001) and body weight (82.6±6 kg before treatment to 78.4±6 kg after treatment, P<0.001).

Significant glucose-lowering activity was noted only in the case group, with fasting blood sugar decreasing from 6.65±0.6 mmol/L before treatment to 6.12±0.5 mmol/L after treatment (P<0.001). There was a significant insulin plasma level reduction only in the case group from 14.47±0.8 μIU/mL before treatment to 9.91±0.7 μIU/mL after treatment (P<0.001). The authors noted a “remarkable” difference in the fasting insulin level between the case and control groups (P<0.001). Homeostasis model (HOMA-IR) was significantly changed only in the case group (from 4.25±0.2 before treatment to 2.67±0.1 after treatment, P<0.001), and there were significant changes between the 2 groups in HOMA index (P<0.001).

Free fatty acid levels were reduced in both groups with significant reductions only in the case group. In the case group, triglycerides decreased significantly (from 2.59±0.6 mmol/L before treatment to 2.24±0.6 mmol/L after treatment, P<0.001); low-density lipoprotein cholesterol (LDL-C) decreased significantly (from 4.05±0.5 mmol/L before treatment to 3.68±0.5 mmol/L after treatment, P<0.001); and high-density lipoprotein cholesterol (HDL-C) increased significantly (1.08±0.1 mmol/L before treatment to 1.29±0.1 mmol/L after treatment, P<0.001). Ceramide levels were reduced markedly only in the case group (8.06±0.2 g/dL before treatment to 6.06±0.3 g/dL after treatment, P<0.001). 

Tumor necrosis factor (TNF)-alpha levels were reduced in both groups, with significant reductions only in the case group (from 1.44±0.2 pg/mL before treatment to 1.41±0.5 pg/mL after treatment, P<0.001). Interleukin-6 levels were reduced in both groups with significant reduction only in the case group (from 1.44±0.3 pg/mL before treatment to 1.09±0.5 pg/mL after treatment, P<0.001). C-reactive protein (CRP) was not significantly reduced in either group. 

Leptin levels decreased in both groups with  significant reductions seen only in the case group (from 13.32±0.2 ng/mL before treatment to 10.84±0.4 ng/mL after treatment, P<0.001). Adiponectin levels were “remarkably” elevated in the case group (7.47±0.2 μ g/mL before treatment to 8.73±0.2 μ g/mL after treatment, P<0.001) and significantly different than the control group. Glucagon-like peptide-1 was also significantly reduced only in the case group (3.77±0.2 mmol/L before treatment to 3.21±0.1 mmol/L after treatment, P<0.001). Resistin levels were significantly reduced only in the case group (from 7.43±0.2 ng/mL before treatment to 5.24±0.3 ng/mL after treatment, P<0.001). Finally, serotonin levels were significantly increased only in the case group (from 130±3 ng/mL before treatment to 170±3 ng/mL after treatment, P<0.001).

This study makes a strong case for the addition of electroacupuncture for obese and overweight people who have been diagnosed with type 2 diabetes and are on first-line therapy with metformin. It shows that electroacupuncture-metformin combined therapy is efficient at promoting weight loss and reducing BMI while exerting significant positive changes in inflammatory markers, adipokines, and lipid markers, all comorbid factors in managing and reversing type 2 diabetes.

 

The results of this study show improvements in all measured parameters in both the case and control groups, but the results were significant only in the case group, with the exception of CRP where no changes were observed. 

 

The effect of the addition of electroacupuncture to metformin monotherapy was impressive. A 9-lb average weight decrease over a 3-week period was observed in the case group compared with a 3-lb average weight decrease in the control group, with commensurate change in BMI of 1.4 kg/m² decrease in the case group compared to 0.5 kg/m² in the control group. Since being overweight or obese is a significant risk factor for developing type 2 diabetes and weight loss has been found to be a significant factor in controlling and reversing it, these study findings alone are encouraging. 

 

With the exception of CRP, all blood sugar markers, lipid markers, inflammatory markers, and adipokines showed positive changes when electroacupuncture was used in addition to metformin. The authors suggest that electroacupuncture may be considered as a new insulin sensitizer.

 

This study gives fresh insights into the efficacy of electroacupuncture on multiple biochemical mechanisms, including lipid metabolism, cytokine function, inflammation, and adipokine production. These mechanisms are poorly understood, but according to the study authors, may include hunger reduction, lipid and carbohydrate metabolism, glucose-inhibited neurons, and feeding behavior.

 

If electroacupuncture is as effective as this study finds in people diagnosed with type 2 diabetes who are on metformin, it makes one wonder how effective the treatment may be on people who are overweight, obese, or otherwise at high risk of developing type 2 diabetes and its associated comorbid conditions.

This study is a pilot study with only 39 total participants. Larger trials are needed to definitively determine the role of electroacupuncture in combination with metformin for overweight/obese patients with type 2 diabetes. Further, this course of treatment was relatively short and treatment frequency was condensed from normal clinical treatment protocols, making it difficult to account for placebo effects, which may have played a role. Meanwhile, the low risk of the therapy and dramatic results suggested by this study can be easily integrated into the care of our patients with type 2 diabetes who are currently on metformin.