by Dr. Takira Glasgow Bsc(McGill), MBBS (UWI), MSc Diabetes with Distinction (UK), MSc Internal Medicine with Distinction (UK), PGDip Obesity and Weight Management (UK)

Weight loss of 15% body weight can prevent progression of pre-diabetes to diabetes and can reverse type 2 diabetes in some cases. Weight loss can also reduce complications of diabetes, cardiovascular risk, significantly reduce medication requirement, and improve quality of life. An emphasis on diabetes prevention in most populations is more cost-effective than treatment. In fact some protocols have introduced weight loss as a primary target of type 2 diabetes management.

There are new medications that may be used in the future for diabetes prevention. These include SGLT-2 inhibitors such as dapagliflozin and empagliflozin; lipase inhibitor orlistat; GLP-1 agonists semaglutide and liraglutide; tirzepatide, a dual GIP/GLP-1 receptor agonist. With the exception of the latter, these medications are available locally but are currently more expensive than Metformin estimated at $30 per month versus Liraglutide at $1200/month.

Some diabetes medications allow weight loss:

• metformin,
• SGLT-2 inhibitors such as dapagliflozin, canagliflozin and empagliflozin,
• SGLT1/SGLT2 inhibitors such as sotagliflozin and licogliflozin,
• pramlintide,
• GLP1 agonists such as semaglutide and liraglutide,
• GLP1/GIP co-agonist tirzepatide,
• GLP1/glucagon dual receptor oxyntomodulin agonist such as mazdutide

Insulin, sulphonylureas, thiazolidinediones and meglinitides may cause weight gain. However, third generation sulphonylureas such as Gliclazide MR and glimepride are recommended above glibenclamide because these are less likely to cause hypoglycaemia (low blood glucose), cardiovascular complications and weight gain. Hypoglycaemia causes weight gain via mechanisms involving hyperphagia (excessive hunger), effects of counterregulatory hormones and lipogenesis (formation of fat).

Some clinical trials:

• Metformin is licensed for pre-diabetes management in the Philippines and Singapore as of 2017. It is used extensively off-label with recommendation from NICE (UK) and ADA (USA) to use clinical judgment with guidance of a diagnosis of obesity, age<60, with impaired fasting glucose and impaired glucose tolerance.
• In the SURMOUNT-1 study, 95.3% of adults with prediabetes treated with tirzepatide versus 61.9% placebo, reverted to normal blood glucose at 72 weeks.
• Meta-analysis of SGLT-2 inhibitors demonstrated relative risk of 0.79 for new onset type 2 diabetes compared to placebo for persons with prediabetes and CKD or heart failure.
• XENDOS, a four year clinical trial compared use of Orlistat plus lifestyle intervention to placebo and lifestyle intervention. The incidence of diabetes after 4 years was 9% with the placebo group and 6.2% with the Orlistat group (risk reduction 37.3%); 11% weight loss from baseline with Orlistat and lifestyle intervention versus 6% with lifestyle intervention plus placebo although there was a greater actual calorie deficit with placebo group.

The size of the population with the pre-diabetes definition can overwhelm both the imagination and the healthcare system, accompanied by the stigma of disease. Critics state that only one third of those diagnosed with pre-diabetes will develop diabetes; pre-diabetes treatment allows the pharmaceutical industry to access a greater number of clients, arguably needlessly, when much can be achieved by public health policies that encourage lifestyle interventions at lower cost. Resources should therefore be allocated appropriately, particularly to higher risk persons such as women with previous gestational diabetes and persons with higher A1c of 6.4 to 6.5%. Moreover, resources should be personalised; weight loss is lower for persons with diabetes compared to persons without diabetes with GLP1 agonists and SGLT2 inhibitors.

Prevent or reverse type 2 diabetes with new weight loss medications? These exciting new medications are noteworthy for weight loss and reduce onset of diabetes and complications, but may be more rationally applicable to diabetes prevention in the future, overcoming concerns about cost and lack of long-term studies.