The rationale for combining GLP-1 receptor agonists with basal insulin.

• Type 2 diabetes mellitus (T2DM) is progressive; the more intensively it is treated, the greater is the risk of hypoglycaemia and weight gain. Achieving treatment intensification while mitigating these risks presents a challenge to patient management. • Basal insulins provide control of fasting glucose; however, their utility in the control of postprandial glucose excursions is limited. • Glucagon-like peptide-1 (GLP-1) receptor agonists stimulate glucose-medicated insulin secretion, suppress glucagon secretion, delay gastric emptying and decrease appetite. Use of GLP-1 receptor agonists in combination therapy with basal insulin offers an alternative approach to intensification of insulin therapy. • Prospective interventional trials demonstrate that GLP-1 receptor agonists added to basal insulin decrease postprandial glucose levels, lower HbA1c levels, decrease weight and lower basal insulin requirements without increasing the risk of major hypoglycaemic events. • The current clinical data are limited by the lack of any data on the long-term effects of GLP-1 receptor agonists over additional prandial regimens; they may be beneficial or deleterious. • Although cost, gastrointestinal side effects and long-term safety should be taken into account when considering this combination, it appears to be growing in popularity and is likely to be an important therapeutic option for T2DM in the future.

Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial.

CONTEXT: Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes. OBJECTIVE: To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. DESIGN, SETTING, AND PARTICIPANTS: Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes. INTERVENTIONS: Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. MAIN OUTCOME MEASURES: Remission of type 2 diabetes (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat. RESULTS: Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval, 2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD) of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R2 = 0.46, P < .001) and lower baseline HbA1c levels (combined R2 = 0.52, P < .001). There were no serious complications in either group. CONCLUSIONS: Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss. These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed. TRIAL REGISTRATION: actr.org Identifier: ACTRN012605000159651.

Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial.

BACKGROUND: Obesity is a major, growing health problem. Observational studies suggest that bariatric surgery is more effective than nonsurgical therapy, but no randomized, controlled trials have confirmed this. OBJECTIVE: To ascertain whether surgical therapy for obesity achieves better weight loss, health, and quality of life than nonsurgical therapy. DESIGN: Randomized, controlled trial. SETTING: University departments of medicine and surgery and an affiliated private hospital. PATIENTS: 80 adults with mild to moderate obesity (body mass index, 30 kg/m2 to 35 kg/m2) from the general community. INTERVENTIONS: Patients were assigned to a program of very-low-calorie diets, pharmacotherapy, and lifestyle change for 24 months (nonsurgical group) or to placement of a laparoscopic adjustable gastric band (LAP-BAND System, INAMED Health, Santa Barbara, California) (surgical group). MEASUREMENTS: Outcome measures were weight change, presence of the metabolic syndrome, and change in quality of life at 2 years. RESULTS: At 2 years, the surgical group had greater weight loss, with a mean of 21.6% (95% CI, 19.3% to 23.9%) of initial weight lost and 87.2% (CI, 77.7% to 96.6%) of excess weight lost, while the nonsurgical group had a loss of 5.5% (CI, 3.2% to 7.9%) of initial weight and 21.8% (CI, 11.9% to 31.6%) of excess weight (P < 0.001). The metabolic syndrome was initially present in 15 (38%) patients in each group and was present in 8 (24%) nonsurgical patients and 1 (3%) surgical patient at the completion of the study (P < 0.002). Quality of life improved statistically significantly more in the surgical group (8 of 8 subscores of Short Form-36) than in the nonsurgical group (3 of 8 subscores). LIMITATIONS: The study included mildly and moderately obese participants, was not powered for comparison of adverse events, and examined outcomes only for 24 months. CONCLUSIONS: Surgical treatment using laparoscopic adjustable gastric banding was statistically significantly more effective than nonsurgical therapy in reducing weight, resolving the metabolic syndrome, and improving quality of life during a 24-month treatment program.

The laparoscopic adjustable gastric band (Lap-Band): a prospective study of medium-term effects on weight, health and quality of life.

BACKGROUND: Obesity is now one of our major public health problems. Effective and acceptable treatment options are needed. The Lap-Band system is placed laparoscopically and allows adjustment of the level of gastric restriction. METHODS: A prospective study of 709 severely obese patients was conducted over a 6-year period at a university-based multidisciplinary referral center. After extensive preoperative evaluation, patients with a body mass index > 35 were treated by Lap-Band placement. Close follow-up with progressive adjustment of gastric restriction continued permanently. Medical co-morbidities were monitored as part of comprehensive prospective data collection. RESULTS: There have been no deaths perioperatively or during follow-up. Significant perioperative adverse events occurred in 1.2% only. Reoperation has been needed for prolapse (slippage) in 12.5%, erosion of the band into the stomach in 2.8% and for tubing breaks in 3.6%. A steady progression of weight loss has occurred through the duration of the study with 52 +/- 19% EWL at 24 months (n = 333), 53 +/- 22% EWL at 36 months (n = 264), 52 +/- 24% EWL at 48 months (n = 108), 54 +/- 24% EWL at 60 months (n = 30), and 57 +/- 15% EWL at 72 months (n = 10). Major improvements have occurred in diabetes, asthma, gastroesophageal reflux, dyslipidemia, sleep apnea and depression. Quality of life as measured by Rand SF-36 shows highly significant improvement. CONCLUSIONS: Placement of the Lap-Band system provides safe and effective control of severe obesity. The effect on weight loss is durable and is associated with major improvement in health and quality of life. It has the potential to provide a broadly acceptable option for this common and serious disease.

Diabetes, psychotic disorders and antipsychotic therapy: a consensus statement.

Psychotic illness and its treatment are associated with an increased rate of diabetes and worsening blood sugar control, Australia. The newer, second-generation antipsychotic agents are more likely to produce this effect than the first-generation agents, but both contribute to the problem. The effect is usually related to insulin resistance through weight gain, but other mechanisms may exist. Diabetic ketoacidosis is rare. Management of psychosis takes priority over concerns about the potential metabolic sequelae of treatment, but the prevalence of the latter requires that all patients taking antipsychotic agents be actively screened and treated. Patients treated with antipsychotic agents need baseline and regular checks, including weight, blood glucose and lipid levels and blood pressure. Management of psychosis with its attendant medical problems requires a multidisciplinary approach, with primary health practitioners playing a central role. Mortality and medical morbidity is higher in those with psychosis than expected; preventive measures, combined with early detection and treatment of hyperglycaemia and other metabolic problems, is a key public health issue.