THE QUEST FOR better treatment for diabetes, which affects more than 420 million people worldwide, continues to drive scientists and doctors toward discovering new drugs. Virtually every year, a couple of new diabetes medications become available for clinical use. In addition, a large number of drugs— more than for any other condition—are in the pipeline. A 2014 US report lists 182 drugs in development for diabetes and its complications. Yet, despite the wide variety of medications available, achieving sustained good control remains a challenge for most people with Type II diabetes.
The first drug discovered for treating diabetes was not an oral agent, but insulin, in 1922, in Canada. Banting, a war hero, tried setting up a practice on the outskirts of Toronto, and in his first year he saw a total of one patient, who came for an alcohol prescription—he therefore decided to pursue academic medicine. Later Banting received the Nobel Prize for his discovery.
The first oral agents used for diabetes were biguanides— derived from a plant, the French Lilac, used to treat diabetes in medieval Europe. Metformin, the most popular and probably safest anti-diabetic drug in use presently, comes from this stable. The second group is the sulfonylureas—discovered in France in 1942 when treating typhoid patients with ‘sulfa’ drugs caused low blood sugar. Sulfonylureas (glimepiride, gliclazide and glipizide) continue to be popular and inexpensive agents, commonly used till date.
When I entered the field of endocrinology in 1980s, these were the two groups of oral drugs that were available to treat diabetes. It was still not established that tight glucose control mattered. With landmark studies like the United Kingdom Prospective Diabetes Study, the importance of achieving better glucose control without getting a low blood sugar reaction (hypoglycemia) was underlined. Hypoglycemia, characterised by intense hunger, sweating, palpitations, and trembling, sometimes with wooziness and loss of consciousness, can be dangerous—particularly for the elderly or those with kidney or heart conditions. Drug development in diabetes over the last two decades has therefore focused on reducing the risk of low blood sugar reactions.
The first among newer drugs were glitazones, which arrived with a bang in the late 1990s. More than a decade after they were launched, glitazones went through a period of complete rejection because of the perceived increase in risk of heart attacks.
Weight loss is one of the major therapeutic approaches to treat and sometimes even cure diabetes. However, many diabetes medications (including sulfonylureas, insulin and glitazones) can cause weight gain, which is counterproductive. ‘Incretin’-based therapies, approved by the FDA in 2006, attempted to address this problem. Incretin based oral medications (DPP4 inhibitors- sitagliptin, vildagliptin, linagliptin, saxagliptin and teneligliptin) rapidly became popular because of the relative lack of side effects. Of these, the first, sitagliptin, has been proven to be safe for the heart in long term studies.
The gamechangers in this regard are the other group of incretin based therapies—the self-injectable GLP1 based drugs. These drugs don’t produce hypoglycemia and promote weight loss. The popular daily injectable GLP1 agonist liraglutide has recently been shown (in the LEADER study) to reduce the risk of heart attacks and deaths. Another exciting development in this group is the convenient once weekly injectable dulaglutide.
A new group of oral drugs, SGLT2 inhibitors (cangliflozin, empagliflozin, dapagliflozin), that control diabetes by throwing out glucose through urine, has hit the headlines recently. Like the GLP 1 therapies, these too, promote weight loss with minimal risk of hypoglycemia. The recently released EMPAREG study showed reduction in risk of deaths and heart failure when high cardiac risk patients were treated with the SGLT2 inhibitor empagliflozin.
While lifestyle modification remains the pivot of diabetes management, it is not sufficient to maintain glucose control in most cases. LEADER and EMPAREG studies have paved the way for an exciting new era in diabetes therapy. However, benefits will accrue only if you adhere to medication schedules. Medications are our ally in the fight against diabetes. Do not fight your medicines, fight your diabetes. So let your doctor choose for you; understand the possible side effects and monitor regularly. Remember: the patient is the key player in the diabetes management team. If you don’t take a drug, it won’t work!