Development of diabetes is an indication that there is some abnormality in the way glucose is handled by different organs, or in the synchrony between them and the hormones. Many organs are involved in regulating blood glucose levels and defect in more than one are present before glucose levels go high-pancreas, liver, kidney, fat, muscle, brain and gut. Although food and activity can help reduce blood glucose to some level in some people with diabetes, others may need medicines. 

“Taking medicines for diabetes is not a sign of failure, it just means that your disease is different from someone else who doesn’t need medicine.“

“Starting  medicines is also not an irreversible event, none of the medicines for diabetes causes addiction and we are often able to stop medicines after starting.” 

“Medicines for diabetes are there to improve healths, they have been rigorously tested for many years before being approved for treatment and their benefits have to outweigh any risk before they are prescribed.“

“Sometimes we have to prescribe medicines for those who have high enough glucose that can damage their organs to reduce glucose, we also need to prescribe medicines which have been proven to reduce risk of heart disease or kidney disease, with the intention of benefitting the patient.” 

“Sometimes we have to de-prescribe medicines, when the risks are higher than benefits, like medicines which can cause hypoglycaemia air low sugar in an elderly person.“

To be able to make right choices about medicines, patients should know the basics of each medicine, their advantages and disadvantages. 

There are eight different types of medicines

Metformin– This is derived from a plant French Lilac plant, hence not all “western medicines” are made in the lab. The origin is from herbal medicine, the only difference between scientifically approved medicines are they have been tested rigorously, whereas many Ayurvedic medicines and some very good ones do not have to undergo that process. We just hope that this artificial chasm between “alternative” and “mainstream” medicine will reduce when we learn from each other.

It mainly acts on the liver to reduce glucose release from liver. (Liver stores glucose in the form of glycogen, which is used when we are in the fasting state like early morning. The amount released is regulated by insulin. Also glucose formation occurs by converting amino acids to glucose a process called gluconeogenesis. If liver is relatively resistant to insulin action, more of glycogen is broken down, releasing more of glucose than required causing high fasting blood glucose). There are other actions as well like improving insulin sensitivity and in the gut.

Metformin does not cause hypoglycaemia by itself (unless given with sulfonylurea or insulin which we will talk about later)

It causes variable amount of weight loss, but no weight gain.

One side effect of metformin is stomach problems, like acidity, flatulence, constipation or diarrhoea, low appetite- which are does dependent. So one usually needs to start from a low dose, and take the medicine in full stomach. 

It is an inexpensive drug.

It is safe for heart and kidney.

Usually this is the first drug to start  in PWD.

Gliptins– these are relatively new class of drugs. These medicines act on the intestine mainly. (Pancreas releases insulin depending on the glucose levels in blood. However, even before food reaches blood in the form of glucose, pancreas gets the information that food has reached the stomach- courtesy signals from the intestine. One of these messengers from gut which warn pancreas in advance and helps regulate glucose efficiently after eating is-GLP1 (glucagon like peptide 1). In type 2 diabetes, GLP1 levels are reduced. GLP1 are very short acting signals because they are destroyed in half an hour by an enzyme called DPP-IV. Gliptins inhibit DPP-IV and hence prolong the effect of GLP1 thus helping to regulate especially postal glucose.)

Gliptins do not cause hypoglycaemia (unless given with sulfonylurea or insulin which we will talk about later)

Gliptins do not cause weight gain.

They are safe for the heart and the kidney.

There are four drugs in this class-Sitagliptin (brand names-Januvia, Istavel); Vildaglitin (There are many brands, some are- Jalra, Galvus, Zomelis, Vylda….); Linaglitin (Brand names- Trajenta, Ondero); Saxagliptin (Brand name- Onglyza).

These drugs have almost similar efficacy. Saxagliptin is not used in heart failure risk patients, and vildagliptin is avoided in liver disease. All of these can be given in kidney disease, some with dose modification. There is cost variation between drugs and brands.

GLP-1 Analogues

These are molecules like GLP1 but longer acting. These are more efficacious than gliptins, because the levels of GLP1 achieved are much higher. At higher levels, GLP1 molecule acts on the satiety centres of brain and reduces appetite and hence are effective in reducing weight as well.

These molecules do not cause hypoglycaemia (unless given with sulfonylurea or insulin which we will talk about later)

They cause significant weight loss, mainly through reduced appetite and reduced gastric emptying. This may also cause certain side effects like nausea, vomitings and diarrhoea, mostly mild. These can be avoided by staring with a low dose of medicine and gradually uptitrating.

These have been shown to reduce the risk of heart disease and kidney disease, independent of glucose control.

Two injectable forms are available

liraglutide (Victoza) which is a daily injection

Dulaglutide (Trulicity, Aplevant) which is a weekly injection

An oral form will be available next year- semaglutide.

These can cause stomach issues like acidity, flatulence, diarrhoea and poor appetite.

SGLT2 inhibitors (Sodium Glucose transporter inhibitors)These are the latest entry in the anti-diabetes field, but have made a dramatic impact not just in the field of diabetes, but also heart failure and kidney disease.

These molecules act on REENTRY GATES for glucose in the kidneys. Glucose which is filtered from kidneys are reabsorbed by sodium-glucose transporters (SGLT-2). When inhibited, the glucose and sodium is lost in urine, thus lowering blood glucose level.

Loss of glucose in urine also results in weight loss

Since only extra glucose is flushed out in the urine, there is nor risk of hypoglycaemia (unless given with sulfonylurea or insulin which we will talk about later)

Since sodium is also flushed out, m it also helps in reducing blood pressure.

In patients with heart failure, heart function improves and mortality is reduced significantly. 

In patients with early kidney disease, it reduces progression of kidney disease.

Since glucose is increased in urine, risk of genital infection is increased. This can be prevented by drinking plenty of fluids.

Since there is loss of carbohydrate or glucose, very very rarely fat oxidation can cause ketoacidosis. This can be risky in insulin deficient patients.

Pioglitazone This is an old molecule, which has seen a lot of ups and downs.

This stimulate PPAR-gamma receptors-these in turn affect formation of certain proteins by genes (transcription). The proteins which are increased include glucose transporters (GLUTs) which we discussed are gates for glucose entry into muscle and other cells. Thus insulin is able to push more glucose inside cells. Pioglitazone is thus an insulin sensitiser. It has additional beneficial effects on fat metabolism.

It does not cause hypoglycaemia (unless given with sulfonylurea or insulin which we will talk about later)

It can cause weight gain.

It causes water retention. Water retention can be an issue in patients with heart failure and kidney failure where this molecule should be avoided,

It can cause bone loss in menopausal women.

Sulphonylureas (SUs)These molecules stimulate insulin secretion from pancreas, and effectively control blood glucose level.

Many SUs have become available for more than 80 years, but we now use mostly newer SUs because of their better safety profile.

The older SUs like glibenclamide (Daonil) have high risk go HYPOGLYCEMIA (Low blood glucose which we have discussed in details elsewhere). The newer molecules we use like Glimepiride (Amaryl, zoryl, GP, Azulix, Glimy…..) and Glibenclamide (Diamicron, Reclide, Cyblex, Glizid….) cause much less hypoglycaemia but the risk is there. That doesn’t mean that we cannot use these molecules, but once we are taking SU, we should monitor glucose weekly and try not to let glucose go below 90 or even 100mg/dl, depending on our individual risk of hypoglycaemia.

The older SUs were also not safe for heart, whereas newer SUs are safe for heart and kidneys. However, we avoid using these in advanced kidney disease because of risk of low sugar.

These are costs effective medicines.

Alpha glucosidase inhibitors

These medicines reduce absorption of carbohydrates from the gut, hence reducing glucose levels after eating. These are especially effective if the carbohydrate content of meals is high.