Diabetes is one of the most common chronic conditions and the treatment options are endless. The medications that are available each work differently with their own effectiveness and side effects.

So how does your doctor determine which medication is the best option for you?

Typically, your doctor will assess your condition holistically and make a decision based on a number of factors, such as:

  • Your blood sugar levels
  • How long you’ve had diabetes
  • How active you are
  • Any other health conditions you suffer from
  • Whether you have a fear of needles
  • Your alcohol consumption

It is important that you adhere to your treatment plan and take medication as prescribed. If you don’t take the correct dose and at the right time, you may suffer from side effects, or your medication may not be as effective as it should be. If you suspect that you suffer from diabetes, you should never self-medicate and rather let your doctor make a formal diagnosis and prescribe the right drugs for you.

So, what are my options?

According to a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes, a tier system is used to prescribe medicines depending on how well the medication has been tested. The tier is divided into steps depending on the patient’s stage of diabetes and how they respond to the lifestyle changes and medicines.

Tier 1:

This includes the most established, effective, and most cost-efficient therapeutic strategies to control blood sugar. This is also the most preferred strategy for patients with type 2 diabetes. The tier is divided into 3 steps.

  • Step 1: These are prescribed at when someone is diagnosed with type 2 diabetes. Apart from a lifestyle change, a mild medication that is well tested, has low and less severe side-effects and is cheap is prescribed.
  • Step 2: A second medication is added when step 1 fails to control blood sugar well enough within 2-3 months of having started step 1.
  • Step 3: When step 2 does not work well enough to achieve the required blood glucose control, injectable insulin is started as step 3. Some medicines may be reduced slowly and then discontinued. A third medication may be added but is not preferred.

Tier 2:

These are less-well tested therapies and are only used under special circumstances. These medicines may have more severe side-effects and are not usually prescribed.

Other:

These are not really preferred as their effectiveness in reducing glucose is lower. They also may have limited clinical data and can be more expensive. Under certain circumstances, these may be the appropriate choice for some patients.

Anti-diabetic medication can broadly be categorized into two classes: oral drugs and injectable drugs.

Oral anti-diabetic drugs include these classes:

  1. Sulphonylureas
  2. Biguanides
  3. Thiazolidinediones
  4. alpha-glucosidase inhibitors
  5. DPP-4 inhibitors
  6. SGLT2 inhibitors
  7. Meglitinides
  8. Bile acid sequestrants
  9. Dopamine-2 agonists

Injectable anti-diabetic drugs include:

  1. Insulin preparations
  2. Glucagon-like peptide 1 (GLP1) agonists

Let’s take a closer look at these medications.

Oral anti-diabetic drugs

Sulphonylureas

Glibenclamide (also known as glyburide), Gliclazide, Glimepiride and Glipizide

Sulfonylureas are the oldest classes of oral diabetes medications and have been available since the 1950s.

How it worksThese drugs lower blood glucose by increasing the amount of insulin the pancreas produces.
EffectivenessModerately effective – 1 to 2% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsSigns of low blood sugar, hunger, skin reactions, upset stomach, dark-colored urine.

Serious side effects: cardiovascular risks, hypoglycemia, weight gain.

Doses and timingGlibenclamide: 2.5-20mg daily in 1-2 divided doses
Gliclazide: 40-320mg daily in 1-2 divided doses
Glimepiride: 1-6mg daily in 1-2 divided doses
Glipizide: 2.5-40mg daily in 1-2 divided doses
Precaution (use cautiously or avoid)Use with care if you have hepatic (liver) or renal (kidney) problems or if you are allergic to sulphonylureas. Consult your doctor before taking any other medication, including anything that seems safe such as aspirin, while taking this class of medicines. This is because these can have interactions with other medicines and can cause dangerous side effects.
Pregnancy category (FDA classification*)C

Glibenclamide is category B.

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Biguanide

Metformin

Metformin is the only biguanide available in the US, and usually the oral treatment choice for type 2 diabetes.

It is also known as an euglycemic agent which means that it may restore the blood sugar to normal or even non-diabetic levels. It helps with weight loss and is the drug of choice for obese patients. It can be taken alone or in combination with other drugs and insulin.

How it worksThis medication reduces the production of glucose by the liver. It also improves how the body responds to natural insulin and decreases the absorption of glucose from the intestines.
EffectivenessVery effective for people with type 2 diabetes. It reduces A1C levels up to 1.5% to 2.0%.
Side effectsLoss of appetite, weight loss, diarrhea, nausea, vomiting, upset stomach, weakness, metallic taste in mouth.

Serious side effects: general feeling of being unwell with severe tiredness, fast or shallow breathing, being cold and a slow heartbeat, the whites of your eyes turn yellow, or your skin turns yellow.

WarningsLactic acidosis may occur in patients with kidney or liver dysfunction, people who take alcohol excessively, have a severe infection or are 65 years or older. Lactic acidosis is a severe and potentially fatal condition where there is a build-up of lactic acid in the body leading to excessive acidity in the body. If you have the following symptoms contact your doctor immediately: nausea, vomiting, unusual muscle pain, stomach pain, rapid/trouble breathing, unusual sleepiness, tiredness, dizziness or feeling cold.
Doses and timing500-850 mg tablet 2-3 times daily.
Precaution (use cautiously or avoid)You should not use metformin if you have severe kidney disease, metabolic acidosis, or diabetic ketoacidosis.

If you need to have any type of X-ray or CT scan using a dye that is injected into your veins (iodinated contrast materials), you may need to temporarily stop taking metformin.

Pregnancy category (FDA classification)B
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Thiazolidinediones

Pioglitozone

Thiazolidinediones used to be widely prescribed, but nowadays only pioglitazone is used. However, this also has been linked with instances of bladder cancer although the evidence was deemed insufficient. However, if you are taking this medication, familiarize yourself aware of symptoms of bladder cancer.

How it worksThese medications improve the way insulin works in the body by increasing the uptake of glucose into muscles, fat, and the liver.
EffectivenessLess effective – 0.5-1.4% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsDiarrhea, nausea/vomiting, upset stomach, muscle pain, headache, sore throat, loss of appetite, back pain, bloating, weakness.

Serious side effects: upper respiratory tract infection, water retention, weight gain, dizziness, fever, abnormal weakness/lack of energy, low white blood cell count, anaemia, hypoglycemia, signs of kidney problems.

Doses and timingPioglitazone: 15-30mg once daily.
Precaution (use cautiously or avoid)These medications may cause or worsen heart failure. Increased risk of becoming pregnant if you are using birth control. It is important to follow any instructions from your doctor about alcohol and other medicines if you are taking these. Make sure that you know what to do if you have fluid retention as fluid retention will increase or lead to heart problems.
Pregnancy category (FDA classification)C (potential risk, better to avoid).
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Alpha-glucosidase inhibitors

Acarbose, Miglitol

These medications are also known as starch blockers. These drugs block the breakdown of starchy foods such as bread, potatoes, and pasta, and they slow down the absorption of some sugars, such as table sugar. You take alpha-glucosidase inhibitors with the first bite of each meal.

How it worksThese medications lower blood glucose by delaying the breakdown of carbohydrates and reducing glucose absorption in the small intestine. They also block certain enzymes to slow down the digestion of some starches.
EffectivenessLess effective – 0.5-0.8% points reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsFlatulence, abdominal bloating, diarrhea.

Serious side effects: potential link to hepatitis (Acarbose).

Doses and timingAcarbose: 50-300mg daily at 3 divided doses.
Miglitol: 25-100 mg 3 times daily.
Precaution (use cautiously or avoid)Do not use these medications if are at risk of intestinal obstruction, or suffer from diabetic ketoacidosis, chronic intestinal disease, colonic ulceration, or inflammatory bowel disease.
Pregnancy category (FDA classification)B
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DPP-4 inhibitors

Vildagliptin, Sitagliptin, Saxagliptin, Linagliptin

These are newer antidiabetic drugs and usually prescribed to type 2 diabetics who do not respond to metformin and sulfonylureas. They promote insulin secretion but because the mechanism is different, they do not cause hypoglycemia.  These drugs may lead to a reduce appetite and weight loss.

How it worksThese medications help your pancreas to release more insulin after meals. They also lower the amount of glucose released by the liver.
EffectivenessLow effective – 0.5-0.8% points reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsStomach problems (nausea, diarrhea, and stomach pain), flu-like symptoms (headache, runny nose, sore-throat) and skin reactions (painful skin followed by a red/purple rash).

Serious side effects: pancreatitis, serious allergic reaction.

Doses and timingVildagliptin: 50mg orally once or twice daily
Saxagliptin: 2.5-5mg daily
Sitagliptin: 100mg orally once daily
Linagliptin: 5mg orally once daily
Precaution (use cautiously or avoid)Avoid if you have a history of inflammation of pancreas (pancreatitis). If you have a severe pain in upper abdomen along with nausea or vomiting, contact the emergency room immediately.
Pregnancy category (FDA classification)N (Not classified).
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SGLT2 inhibitors

Canagliflozin, dapagliflozin

SGLT2 stands for Sodium-glucose co-transporter-2. It is a protein that transports glucose back to the blood from the kidney. They work by reducing the absorption of glucose from the fluid that is filtered from the blood by the kidney, causing more glucose to be eliminated in the urine. These medications increase urinary glucose excretion and consequently lower blood sugar levels. Because they increase glucose levels in the urine, side effects can include urinary tract (UTI) and yeast infections.

How it worksThese drugs work on the kidneys to remove extra sugar from the body.
EffectivenessLess effective – 0.5 to 1% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsHypoglycemia, UTI, genital infection, lose bone density, dehydration.

Serious side effects: amputations, kidney failure, high potassium levels and ketoacidosis.

Doses and timingDapagliflozin: 5-10mg once daily before breakfast
Canagliflozin: 100-300mg once daily before breakfast.
Precaution (use cautiously or avoid)Severe renal impairment, frequent ketones in blood or urine, elderly patients. If you are taking this medication, your urine will show glucose in urine almost all the time when you check with urine glucose strips – this is a normal happening with this medication.
Pregnancy category (FDA classification)C
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Meglitinides

Repaglinide, Nateglinide

These drugs are not members of sulphonylureas but have a similar mechanism of action. Meglitinides start to work very soon after they are taken but last for only a short time. These are prescribed to limit the spikes in blood glucose after meals. These are suitable for people with non-routine lifestyles, so they can take this medicine whenever they take food.

How it worksThese medications lower blood glucose by getting the pancreas to release more insulin.
EffectivenessLess effective – 0.5 to 1.5% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsLow blood glucose, headache, cold symptoms like a stuffy nose and sneezing, and back pain, liver problems, stomach pain, nausea, diarrhea, constipation, weight gain, blurred vision.

Serious side effects: severe allergic or skin reaction.

Doses and timingRepaglinide: 0.5-16mg daily in 3 divided doses prior to meals.
Nateglinide:60-180mg daily in 3 divided doses prior to meals.
Precaution (use cautiously or avoid)Do not use this medication if you suffer from severe liver disease. Patients under 18 years old should not use these drugs.

These medications can interact with alcohol to cause vomiting, flushing, or sickness.

Pregnancy category (FDA classification)C
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Bile acid sequestrant

Colesevelam

This cholesterol-lowering medication also reduces blood glucose levels in patients with diabetes. Bile acid sequestrants help remove cholesterol from the body, particularly LDL cholesterol, which is often elevated in people with diabetes. The medications reduce LDL cholesterol by binding with bile acids in the digestive system. The body then uses cholesterol to replace the bile acids, which lowers cholesterol levels. The exact way these agents lower blood glucose is well understood.

Bile acid sequestrants are not absorbed into the bloodstream, so they are usually safe to use by patients who may not be able to use other medications because of liver problems.

How it worksThe medications bind with bile acids in the digestive system. The body then uses cholesterol to replace the bile acids, which lowers cholesterol levels, and in turn glucose levels.
EffectivenessLess effective.
Side effectsConstipation, stomach pain, bloating, vomiting, heartburn, loss of appetite, indigestion, and upset stomach.

Severe side effects: severe abdominal pain with or without nausea and vomiting.

Doses and timing3.75g (six 625 mg tablets) in 1 or 2 divided doses.
Precaution (use cautiously or avoid)These medications should be avoided if you suffer from pancreatitis, have a history of bowel obstruction, high triglycerides or decreased gastrointestinal motility.
Pregnancy category (FDA classification)C

Dopamine agonist

Bromocriptine

Bromocriptine differs from other antidiabetic drugs in that it reduces blood glucose through the central pathways. These medications help lower blood glucose levels after a meal.

How it worksThe exact way how dopamine agonists reduce blood glucose is unknown.
EffectivenessLess effective – 0.4 to 0.8% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsNausea, vomiting, diarrhea, constipation, stomach cramps, heartburn, loss of appetite, headache, weakness, tiredness, dizziness or light-headedness, drowsiness, difficulty falling asleep or staying asleep, depression

Serious side effects: fainting, black/tarry stools, bloody vomit or if it looks like coffee grounds, numbness/tingling, swelling, severe headache, blurred/impaired vision, chest pain, shortness of breath, seizures, confusion, hallucinations.

Doses and timing0.8 mg once a day, within two hours after waking up in the morning
Precaution (use cautiously or avoid)Tell your doctor if you:

  • have high or low blood pressure or migraine headaches that cause fainting.
  • are having surgery, including dental surgery.
  • develop intense urges or behaviors that are compulsive or unusual, such as gambling, increased sexual urges or behaviors, and excessive shopping.
  • have heart disease or have ever had a heart attack, a slow, fast, or irregular heartbeat.
  • have mental illness.
  • have ulcers or bleeding in the stomach or intestines.
  • have kidney or liver disease.
  • have or any condition that prevents you from digesting foods containing sugar, starch, or dairy products normally.
Pregnancy category (FDA classification)B

Injectable anti-diabetic drugs

Insulin preparations

There are many types of insulin preparations available in the market. They differ from each other in terms of efficacy and duration of action. These preparations can be categorized into 4 groups based on how fast they work: short acting, intermediate acting, long acting and fast acting.

  • Short-acting insulin

Humulin R

Regular (soluble) insulin or Insulin-R is the short acting insulin which acts within 30 minutes to 1 hour. They reach a peak in around 1-4 hours and lasts for 4-8 hours. This type of insulin may be prescribed in some cases during the initial therapy along with food. Regular insulin can be given intravenously and is the drug of choice in critically ill or hospital-bound patients. It may cause hypoglycemia and needs to be taken 30 min to 1 hour before a meal. This type is usually given together with intermediate or long-acting insulin.

How it worksIt works by helping blood sugar (glucose) get into cells so your body can use it for energy.
EffectivenessVery effective – 1.5 to 3.5% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsHypoglycemia, lipodystrophy (abnormal mass of fat under the skin) at the injection site, weight gain.

Serious side effects: low potassium levels (muscle cramps, weakness, irregular heartbeat), heart failure.

Doses and timingThe dose depends on blood sugar level. Should be taken 30 minutes before each meal.
Precaution (use cautiously or avoid)Do not use this medication if you suffer from hypoglycemia.
Pregnancy category (FDA classification)B
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  • Intermediate-acting insulin

Humulin N, Insulin NPH, Novolin N

Also known as isophane insulin or NPH (Neutral Protamine Hagedorn), these are intermediate-acting insulins. They take 1-3 hours to start acting, reaches a peak at 4-8 hours and lasts for 7-14 hours. When patients are started on insulin, this is the one that is preferentially prescribed to increase the basal levels of insulin.

How it worksStimulates glucose uptake by the cells and reduces blood glucose levels.
EffectivenessVery effective – 1.5 to 3.5% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsLow blood sugar, weight gain, swelling, allergic reaction as injection site.

Serious side effects: fluid retention, low potassium levels.

Doses and timingDose needs to be individualized and is usually given at bedtime or with breakfast.
Precaution (use cautiously or avoid)Do not use if you suffer from hypoglycemia. Use with caution in renal and hepatic impairment.
Pregnancy category (FDA classification)B
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  • Long-acting insulins

Insulin Glargine, Insulin Degludec, Insulin Detemir

Long-acting insulins do not have a peak like shorter-acting insulins. They typically reach the bloodstream several hours after injection and work to lower glucose levels for around 18 – 24 hours. These are often combined with rapid- or short-acting insulin.

How it worksStimulates glucose uptake by cell and reduces blood glucose level. Has a long half-life and works for a prolonged period.
EffectivenessVery effective – 1.5 to 3.5% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsHypoglycemia, lipodystrophy (abnormal mass of fat under the skin), allergic reaction.

Serious side effects: low potassium, rapid weight gain, swelling in hands and feet, breathing problems.

Doses and timingDose needs to be adjusted for the individual patient. Usually, 0.1-0.2 IU/kg in the evening.
Precaution (use cautiously or avoid)Do not use if you suffer from hypoglycemia or diabetic ketoacidosis.

Use with caution if you have liver or kidney disease or failure/other heart problems.

Pregnancy category (FDA classification)Insulin detemir and insulin glargine: B
Insulin degludec: C
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Insulin Glargine

  • Lantus
  • Basaglar
  • Toujeo

Insulin Degludec

  • Tresiba

Insulin Detemir

  • Levemir
  • Fast-acting insulin

Insulin Lispro, Insulin Aspart, Insulin Glulisine

These medications are termed as rapid acting because they start acting within 15 – 30 minutes. They reach a peak in 30 minutes – 2.5 hours and lasts for about 3-4.5 hours. These medications are often used with long-acting insulins.

How it worksIt replaces the insulin that is normally produced by the body and helps sugar movement from the blood into other body tissues to use for energy.
EffectivenessVery effective – 1.5 to 3.5% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsHypoglycemia, weight gain, swelling of hands/feet, lipohypertrophy.

Serious side effects: low potassium levels, heart symptoms (e.g., fast and irregular heartbeat), vision changes (e.g., vision loss or blurred vision), severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, stiff muscles, high fever, profuse sweating, or tremors.

Doses and timingUsual range is 0.5-1 IU/kg/day. Must be given with a meal, or just before or after a meal.
Precaution (use cautiously or avoid)Liver or kidney impairment.
Pregnancy category (FDA classification)B
For Insulin Glulisine: C
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Insulin Aspart

Insulin Glulisine

Glucagon-like peptide 1 (GLP1) agonists

Liraglutide, Exenatide

GLP1s are very effective at lowering blood sugar levels, and some have also shown benefits for heart health and kidney function.

These medications also induce weight loss, so it is an appealing therapy for obese patients.

How it worksSlows down digestion to prevent blood sugar from spiking after a meal.

Helps the body make more insulin.

Reduces the release of sugar from the liver.

EffectivenessLess effective – 0.5 to 1% point reduction in level of glucose bound to hemoglobin (A1C levels).
Side effectsNausea, diarrhea, vomiting, loss of appetite.

Serious side effects: ongoing abdominal pain, skin rash/hives/itching, pounding heart, dizziness/fainting, swelling, trouble breathing, hoarseness, decreased urination, dry mouth/skin, extreme thirst

Doses and timingLiraglutide: 0.6-1.8 mg subcutaneously once daily
Exenatide: 5mcg 12 hourly within 60 minutes of meal.
Precaution (use cautiously or avoid)Use with caution if you have a history of pancreatitis, gastroparesis (paralysis of the stomach), thyroid cancer, are on dialysis.
Pregnancy category (FDA classification)C
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Exenatide

  • Byetta
  • Bydureon

*FDA pregnancy categories

The FDA has established five categories to show the possibility of a drug to cause birth defects if used during pregnancy. These categories are determined by the reliability of documentation and the risk to benefit ratio (whether benefits are more than the risk or vice-versa). They do not consider any risks from pharmaceutical agents or their metabolites in breast milk. The pregnancy categories are:

Category A

Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy and there is no evidence of risk in later trimesters.

Category B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Category C

Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category D

There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category X

Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.]

Category N

FDA has not classified the drug.