Though not discussed as much as other chronic illnesses, obesity is actually the mother of all diseases. Adults are considered obese when their body mass index (BMI) is above a particular cut-off. For Indians, the cut-offs in kg/m2 are 23-24.9 for “overweight” and 25 for “obese.” A waist circumference of 80 cm in women and 90 cm in men is considered high. Others use waist-to-hip ratio to define central obesity. According to World Health Organisation figures, obesity has increased exponentially worldwide, tripling since 1975.
HOW OBESITY UPS DIABETES RISK
There is a strong link between increasing obesity and Type 2 diabetes, which operates at multiple levels. First, if you are overweight or obese, your risk of developing diabetes is significantly higher. The overall risk of developing diabetes is six times higher in those with excess body weight. In a UK study, the group with a mean BMI of 34.5 was associated with a 12-fold higher risk than the lean group. So, if you are looking to prevent diabetes, watch your waist! Second, if you have diabetes, obesity makes it difficult to control blood sugar, and your requirement for medication will increase incrementally. Third, obesity worsens diabetes complications. For example, your risk of having a heart attack is increased if you have obesity with diabetes rather than just one of these conditions.
Numerous studies have shown that weight reduction can favourably impact all the conditions listed above. You can reduce your chances of developing diabetes, simplify your diabetes management, and reduce the risk of complications. Not just that, weight reduction early in the course of diabetes can free you of medication, that is induce remission or reversal of your condition, particularly in young individuals.
That brings us to the million dollar question: How does one lose weight? Everyone will agree that shedding those kilos can be a hugely challenging, and often, a highly frustrating task. The key to weight loss is lifestyle modification, which essentially means diet and exercise. Both of these entail behavioural modification, which is difficult to implement, and even more difficult to sustain. For those people with diabetes, who meet the criteria, bariatric surgery is an option. But what about medication? Unfortunately, some of the conventional medications for diabetes – like Sulphonylureas, Thiazolidinediones and insulin – are associated with weight gain rather than weight loss. Others like Gliptins (DPP4i) are weight-neutral. Metformin is the only conventional agent associated with weight loss but the effect is small.
SO WHAT’S THE GOOD NEWS?
Over the last 10 years or so, there has been a paradigm shift in the treatment of diabetes. This has been made possible with the discovery of new classes of agents like SGLT2 inhibitors and GLP1 receptor agonists. SGLT2 inhibitors are oral agents, freely available in India (Dapagliflozin, Empagliflozin, Canagliflozin, Remogliflozin) that eliminate glucose through the urine, do not produce low blood sugar reactions and help in weight loss. Typical weight loss with these agents ranges from 2 to 3 kg. This may not seem much but is significant in terms of its health benefits, as it makes diabetes easier to control and reduces the risk of complications. These drugs also reduce the risk of heart failure, heart attacks and kidney failure by their direct actions on these organs. These characteristics have resulted in a remarkable rise in popularity and widespread use of these drugs.
The other group of anti-diabetic drugs which induces weight loss while lowering blood sugar is the “GLP1 RA”, such as Liraglutide, Dulaglutide, and now Semaglutide. Liraglutide and Dulaglutide are injected (daily and weekly, respectively) by a pre-filled, easy to use syringe. GLP1 RA act to reduce weight primarily by their actions on the brain, wherein they reduce appetite and induce satiety. The resultant weight loss is slightly greater than that seen with SGLT2 inhibitors, often in the zone of 2 to 4 kg, although there is considerable inter-individual variability. The biggest challenge to the use of these molecules was the need for injections, a problem that has been circumvented with the availability of oral Semaglutide in India.
Impressive as the data are, the weight loss effects of these drugs used alone can best be described as moderate. Combining medications from both the groups results in an average weight loss of up to 5 kg.
Disappointed? Well, there is more good news. Although not yet available in India, injectable Semaglutide (as opposed to oral, which is available in India) given in a dose of 2.4 mg weekly can result in a mean weight loss of 15 kg over 7 months in those without diabetes. The figures for those with diabetes are slightly lower.
Most participants (70 per cent to 80 per cent) lose five per cent or more of their body weight. As if this was not enough, dual GIP/GLP-1 RA agonist Tirzepatide (also not available in India yet) given as a weekly injection of 15 mg, was shown to produce a 3 to 5 kg greater weight loss than a weekly injection of Semaglutide 2 mg.
THE CHALLENGE OF NOT REGAINING WEIGHT
This degree of weight loss — induced by what were primarily developed as diabetes medications — was unimaginable even five years ago. However, weight regain on treatment discontinuation remains a challenge unless the individual is disciplined with regard to diet and exercise. If you are willing to watch what you eat, and move your body, these new anti-diabetes medications will help you fight that flab.