MetaCure

History

Founded in 2003 by Dr. Shlomo Ben-Haim, MetaCure has developed an implantable medical device system for the treatment of type 2 diabetes and obesity. The company’s DIAMOND System (formerly called Tantalus) uses a platform technology that provides non-excitatory (non-pacing) stimulation to tissue that produces a physiological response. The electrical stimulation, which is applied to the stomach muscles, is called gastric contractility modulation (GCM). Through GCM, DIAMOND improves how glucose is metabolized in the body. This platform technology was first applied to the treatment of heart failure. When applied to heart tissue, the electrical stimulation is known as cardiac contractility modulation.

MetaCure is one of the portfolio companies of the Hobart Group, which invests in medical device companies.

Type 2 Diabetes and Obesity

The International Diabetes Federation estimates that diabetes affects 566 million people worldwide, with 90%-95% of people having type 2 Diabetes. The prevalence of diabetes is expected to increase to over 770 million in 2035. This rise in prevalence is expected to occur because of the global obesity epidemic. Obesity is a major risk factor for the onset of diabetes. In fact, obesity and abdominal fat is thought to account for 80%-90% of type 2 diabetes cases, which has led to the creation of the term “diabesity”. The World Health Organization (WHO) estimates that more than 60% of adult Americans and approximately half of female Europeans are overweight and obese.

Treatment goals

Controlling post-prandial blood glucose concentration is a primary treatment goal for type 2 diabetes. Blood glucose concentration is assessed by measuring the amount of glycated hemoglobin (HbA1c) in the blood. The UK Prospective Diabetes Study (UKPDS) found that a 1% reduction in HbA1c lowers the risk for diabetes-related mortality by 21% and myocardial infarction (MI) by 14%. Reducing HbA1c by 1% also lowers the risk of microvascular complications, such as amputation of a limb, which is a common complication of diabetes.

Types of treatment

After failing dietary and lifestyle counseling, most patients with diabetes are initially treated with oral medication, such as metformin. As diabetes is progressive, most patients will need treatment intensification to achieve HbA1c targets. Treatment intensification may include the addition of other oral medications, insulin, or another injectable treatment, glucagon-like peptide receptor agonists (GLP-1 RAs). Patients who are also obese may be referred for bariatric surgery.

Anti-diabetic treatments have varying degrees of effectiveness in lowering HbA1c. Effectiveness of any medication is also affected by a patient’s treatment adherence. Insulin, which is injected by the patient with a needle or a pen-like device, is most effective at lowering HbA1c. However, insulin has two notable side effects - hypoglycemia and weight gain – that can be a challenge to manage and have clinical consequences.

The DIAMOND System

The DIAMOND System was developed to address the gaps in existing treatment options for obese patients with diabetes. It is thought that the use of gastric contractility modulation (electrical stimulation of the stomach), enabled by a one-time, minimally invasive procedure with minimal complications, no dietary restrictions, and negligible patient adherence requirements, could address the clinical challenge of treating patients with type 2 diabetes. DIAMOND II is a medical device system that consists of an implantable pulse generator, electrodes, a programmer, and a patient charger.

Mechanism of Action

The mechanism by which DIAMOND’s gastric contractility modulation (GCM) improves blood glucose concentration and induces weight loss is being investigated. It is hypothesized that DIAMOND corrects the body’s natural metabolism processes by resynchronizing the timing of the gut-brain-liver axis activation with food intake. Once food leaves the stomach and enters the duodenum, the gut-brain-liver axis is activated, which involves signaling between the gastrointestinal tract and the nervous system. For patients without type 2 diabetes, the gastric transit time of food is estimated to be 30–45 minutes (the time from food ingestion to food leaving the stomach into the duodenum). In type 2 diabetes, the neurohormonal communication system is impaired. Delayed signaling within the gut-brain-liver axis leads to high blood glucose concentration after meals.

DIAMOND uses an algorithm that allows it to automatically detect food intake. When DIAMOND senses that food has entered the stomach, energy from a rechargeable pulse generator is transmitted to electrodes attached to the gastric antrum. DIAMOND provides non-excitatory electrical stimulation, which causes increased contractile force to each of the naturally occurring rhythmic stomach contractions (normal stomach peristalsis). In this way, DIAMOND strengthens stomach contractions to a similar level that occurs when the normal stomach is emptying the food content into the duodenum. The stronger antral contractions activate the gut-brain-liver axis just as they do normally when food is entering the duodenum. Signals are sent from the stomach along afferent vagal nerve fibers to the hypothalamus, which interprets the signals to mean that food has departed the stomach. In this way, DIAMOND induces early satiety. The hypothalamus also sends signals to the pancreas to release insulin and to suppress glucagon. Signals are also sent to the liver to stop production of glucose and start using glucose to synthetize glycogen. In this way, DIAMOND resynchronizes the metabolic response to food intake and improves blood glucose levels.

DIAMOND Implantation

DIAMOND is implanted during a minimally invasive, laparoscopic procedure. The electrodes that detect food intake are attached to the surface of the gastric fundus. The electrodes that provide stimulation are attached to the gastric antrum. The pulse generator is housed in a surgically created pocket in subcutaneous tissue in the upper left area of the abdomen (similar to a standard pacemaker implantation). The procedure does not entail any changes to the stomach’s anatomy, which means that the procedure is reversible, i.e., DIAMOND II can be explanted.

Clinical data

The efficacy and safety of DIAMOND has been examined in several clinical trials, including two randomized controlled trials, a long-term study, and an insulin comparative study. The various clinical studies have demonstrated that DIAMOND therapy has several metabolic benefits, including blood glucose control, weight loss, reduction in waist circumference, and blood pressure, that have been sustained for a minimum of three years. DIAMOND also had favorable outcomes compared to insulin therapy in a randomized controlled trial. The DIAMOND procedure is safe and well tolerated, according to clinical trial investigators.

Efficacy

In a multicenter, open-label study, 24 obese patients with diabetes received laparoscopic implantation of Tantalus-DIAMOND. At one-year follow up, DIAMOND resulted in significant reductions in weight and HbA1c (P<0.05). A later analysis of 50 patients treated with oral antidiabetic medication showed that 80% of the cohort experienced HbA1c improvement, with an average decline of 1.1% at 24 weeks. The mean weight loss was 5.5 kg.

In an analysis of 61 diabetic patients that failed oral medication for treating their diabetes, the HbA1c reduction averaged 0.9%. In patients with normal triglycerides, the HbA1c was reduced by 1.1% during three years of follow up. The mean weight loss for the entire cohort was 5.7%. Weight loss of more than 10% was experienced by a significant percentage of patients with normal triglyceride levels and maintained to three years A separate randomized blinded cross-over trial of 51 patients has also shown that GCM accounts for significant improvement in HbA1c.

DIAMOND’s GCM has also been compared to insulin in 16 obese diabetic patients on oral medication who needed treatment intensification. Patients were randomized to receive implantation of DIAMOND or to an insulin treatment group. At one year follow up, patients who were treated with DIAMOND’s GCM experienced an average weight loss of 3.2 kg and reduction in waist circumference of 3.8 cm. Comparatively, patients treated with insulin gained 1.4 kg on average. Patients treated with DIAMOND also had greater reduction in HbA1c than those treated with insulin at 1.6% and 0.6%, respectively. DIAMOND also resulted in systolic blood pressure improvement of 4.5 mmHg, whereas patients in the insulin arm had an increase of 2.3 mmHg on average.

Safety

The adverse event rate for implantation of the DIAMOND II System is similar to that for other common laparoscopic procedures, such as transient post-procedure abdominal pain, and have been reported to be mild.

Medical uses

The DIAMOND system first received CE mark in 2007 and is approved for sale in Europe, Australia, Hong Kong, and other international markets. DIAMOND is currently not available for use in the United States.