For diabetic mellitus, a variety of drug kinds are accessible; each has a unique mode of action and set of side effects. A physician evaluating the patient’s health should select the optimal medication; keep in mind that all of these are prescription medications that must be taken correctly, under medical supervision, with the recommended dosage, and at the appropriate times. It is imperative that you always do as your doctor says. Never take medication by yourself.
Anti-diabetic medications can be broadly divided into two classes:
A. Oral medications for diabetes:
The following classes are included in this:
- Insulin secretagogues: glycosides/meglitinides, which are non-sulphonylureas, and sulphonylureas
- Biguanides
- Diazozolidinediones
- Inhibitors of a-glucosidase
- Di-peptydyl Gliptins and peptididase-4 (DPP-4) inhibitors
- Inhibitors of the sodium-glucose co-transporter 2 (SGLT2)
B. Anti-diabetic injectable medications:
- Insulin getting ready
- Agonists for glucagon-like peptide 1 (GLP1)
A tier system is used to prescribe medications according on how validated (tested) the treatment is, according to a consensus statement from the European Association for the Study of Diabetes and the American Diabetes Association. Depending on the patient’s response to medication and lifestyle modifications, as well as the patient’s stage of diabetes, the tier is divided into steps.
Tier 1: This comprises the most well-proven, economical, and efficient therapeutic approaches for blood sugar regulation. Patients with type 2 diabetes also favor this approach the most. There are three steps in the tier.
Step 1: When a person is diagnosed with type 2 diabetes, these are prescribed. In addition to a change in lifestyle, a light drug that is inexpensive, well-tested, and has few to no side effects is administered.
Step 2: When step 1 doesn’t sufficiently manage blood sugar within two to three months of starting step 1, a second drug is added.
Step 3: Injectable insulin is started as a backup plan when step 2 is insufficiently effective in achieving the necessary blood glucose control. Certain medications may also be gradually tapered off before being stopped altogether. Although it is not recommended, a third medicine may be added.
Tier 2: These treatments have not been as well studied and are only applied in specific situations. These medications are typically not administered since they may have more serious side effects.
Other: These are less desirable because they don’t do as well at decreasing blood sugar. They could also cost more and have less clinical evidence. For certain folks, they might be the best option, though, depending on the situation.
Let’s review these medications in brief:
Tier 1, Step 1:
Biguanide:
Since it doesn’t alter the body’s insulin levels, metformin—the only biguanide that is widely accessible—is not likely to result in hypoglycemia. Another name for it is a “euglycemic agent,” which indicates that it has the ability to bring blood sugar levels back to normal or non-diabetic levels. It is the medication of choice for obese patients and helps with weight loss. It can be used either on its own or in conjunction with insulin and other medications.
| How it works | Decreases glucose production by liver. Delays intestinal absorption of glucose. Increases uptake of glucose. |
| Effectiveness | Moderately effective – 1 to 2% point reduction in level of glucose bound to hemoglobin (A1C levels). |
| Convenience | Very convenient. |
| Side effects | Loss of appetite, weight loss, diarrhea, nausea, vomiting, stomach- upset, weakness, metallic taste in mouth. Please contact your doctor if any of these last for a longer time or become worse. WARNING: Lactic acidosis may occur in patients with kidney or liver dysfunction or in people who take alcohol excessively. Lactic acidosis is a severe and potentially fatal condition where there is a buildup 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, generalized muscle weakness/cramping, rapid breathing, unusual sleepiness, tiredness. |
| Doses and timing | 500-850 mg tablet 2-3 times daily. |
| Precaution( use cautiously or avoid) | Kidney impairment, general anesthesia, X-ray or scanning using iodinated contrast materials. The elderly above age 80 are at a higher risk of getting side effects – they should have a kidney function test before taking this medication. |
| Pregnancy category(FDA classification) | B |
| Cost | 100 tablets $10 – $16. |
Tier 1, Step 2:
A) Sulphonylureas:
They primarily serve as metformin’s adjuvant therapy. They cause weight gain and are not recommended for patients who are obese. Each person responds differently to this class of medicines in terms of effectiveness and adverse effects. Glibenclamide, sometimes referred to as glyburide, gliclazide, glimepiride, and glipizide are the sulphonylureas that are most frequently utilized.
| How it works | Insulin secretagogues – Promotes insulin secretion acting on beta cells of pancreas. This action is independent of glucose. |
| Effectiveness | Moderately effective – 1 to 2% point reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Very convenient. |
| Side effects | Hypoglycemia (especially with longer acting sulphonylureas like chlorpropamide and glienclamide, in people who eat irregularly and in people who drink alcohol excessively), weight gain, stomach upset, increased sensitivity to light. Rare side effects: liver problems which may lead to jaundice, allergic reaction (itchy red skin or rashes), anemia, thrombocytopenia (reduction in the number of platelet cells in the blood which leads to increased bruising), andsevere reduction in the number of white blood cells.. |
| Doses and timing | Glibenclamide: 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 cautiously in hepatic (liver) or renal (kidney) impairment. Should be avoided in case of allergy to sulphonylureas. Consult your doctor before taking any other medication (including anything that seems safe – like aspirin) while taking this class of medicines. This is because these can have interactions with other medicines which can be dangerous. |
| Pregnancy category (FDA classification*) | CGlibenclamide is category B. |
| Cost | 100 tablets $11 – $32. |
B) Preparations for insulin:
Insulin can be used as an additional therapy in tier 1, step 2, to lower blood glucose levels to normal. When a patient with type 2 diabetes is unable to take sulfonylureas for any reason, this is typically recommended at this point. When supplemental medication is unable to lower blood glucose, metformin and intense insulin treatment are used in tier 1, step 3. The market is filled with several kinds of insulin formulations. Their duration of action and effectiveness are different from one another. Based on how quickly they act, these preparations can be divided into four groups: short acting, intermediate acting, long acting, and rapid acting. These insulins are used together to form biphasic insulins.
Acting quickly, insulin:
The short-acting insulin, known as regular (soluble) insulin or Insulin-R, begins to operate in 0.5–1 hour, peaks in 1-4 hours, and lasts for 4–8 hours. In certain situations, during the first therapy, this kind of insulin may be recommended in addition to meals. For critically ill or hospitalized patients, regular insulin is the preferred medication that can be administered intravenously. It must be taken 30 minutes to an hour before a meal because it may result in hypoglycemia. Insulin that acts slowly or long-acting is typically administered in combination with this type.
| How it works | Stimulates glucose uptake by cell and reduces blood glucose level. |
| Effectiveness | Very effective – 1.5 to 3.5% point reduction in level of glucose bound to hemoglobin(A1C levels) |
| Convenience | Less convenient. |
| Side effects | Hypoglycemia, lipodystrophy (abnormal mass of fat under the skin), allergic reaction. |
| Doses and timing | The dose depends on blood sugar level. Should be taken 30 minutes before each meal subcutaneously. |
| Precaution( use cautiously or avoid) | Adjust dose requirement cautiously to prevent hypoglycemia. |
| Pregnancy category(FDA classification) | B |
| Cost | 3 ml penfill $4-$5. |
- Insulin that acts intermediately:
These intermediate-acting insulins are sometimes referred to as isophane insulin, NPH (Neutral Protamine Hagedorn), or lente insulins. The action begins in one to three hours and lasts for seven to fourteen hours, peaking between four and eight hours in. This is the type of insulin that is preferentially provided to patients to raise their basal insulin levels when they first start taking it.
| How it works | Stimulates glucose uptake by cell and reduces blood glucose level. |
| Effectiveness | Very effective – 1.5 to 3.5% point reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Convenient. |
| Side effects | Hypoglycemia, lipodystrophy(abnormal mass of fat under the skin), allergic reaction. |
| Doses and timing | Dose needs to be individualized. Is usually given at bedtime or with breakfast, |
| Precaution( use cautiously or avoid) | Pregnancy and renal impairment. |
| Pregnancy category(FDA classification) | B |
| Cost | 3 ml penfill $4. |
- Long-acting insulins:
The extended half-lives of insulin glargine, insulin degludec, and insulin temir are 18 to 24 hours. Although the duration of action of bovine Ultralente insulin is likewise longer, allergic responses limit its use. Since this type of insulin is only administered once or twice a day, patients have considerably improved insulin usage.
| How it works | Stimulates glucose uptake by cell and reduces blood glucose level. Has a long half-life and works for prolonged period. |
| Effectiveness | Very effective – 1.5 to 3.5% point reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Very convenient. |
| Side effects | Hypoglycemia, lipodystrophy(abnormal mass of fat under the skin), allergic reaction. |
| Doses and timing | Dose need to be adjusted for the individual patient. Usually, 0.1-0.2 IU/kg subcutaneously at evening. |
| Precaution( use cautiously or avoid) | Renal and hepatic impairment. |
| Pregnancy category(FDA classification) | Insulin detemir and insulin glargine: B Insulin degludec: C |
| Cost | 3 ml catridge $13-$15Insulin degludec $28-$30. |
- Fast-acting insulin:
Because of their quick start of action, insulins Lispro, Aspart, and Glulisine are referred to as rapid acting. Their 30-minute anti-glycemic effect intensifies over the next 0.5–2.5 hours, peaking in 3–4.5 hours.Those with type 1 diabetes are typically prescribed these, however occasionally type 2 diabetics are prescribed these in addition to other types of insulin.
| How it works | Stimulates glucose uptake by cell and reduces blood glucose level. |
| Effectiveness | very effective – 1.5 to 3.5% point reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Less convenient. |
| Side effects | Hypoglycemia, lipohypertrophy (abnormal mass of fat under the skin), hypersensitivity. |
| Doses and timing | Usual range is 0.5-1 IU/kg/day. Need to be given subcutaneously with a meal (just before or after a meal). |
| Precaution(use cautiously or avoid) | Kidney impairment, infection. |
| Pregnancy category(FDA classification) | B But for Insulin Glulisine: C |
| Cost | 3 ml penfill $8-$15. |
- Preparations of mixtures or biphasic insulin:
These are mixtures of NPH insulin and soluble insulin in varying amounts, or NPH insulin and a fast-acting insulin analog. The most popular formulation is a 30/70 ratio of isophane insulin to regular insulin. Premixed insulins such as Insulin Lispro + Protamine, Insulin Degludec + Insulin Aspart 70/30, and Insulin Aspart biphasic are among the other widely used formulations.
| How it works | Stimulates glucose uptake by cell and reduces blood glucose level. |
| Effectiveness | Very effective -1.5 to 3.5% point reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Very convenient. |
| Side effects | Hypoglycemia, weight gain, lipodystrophy(abnormal mass of fat under the skin), allergic reaction. |
| Doses and timing | Varies according to patients’ condition. Usually ⅔rd of daily dose at morning and ⅓rd at evening. |
| Precaution (use cautiously or avoid) | Kidney or liver impairment. |
| Pregnancy category(FDA classification) | Depends on the components of the combination. |
| Cost | Varies according to combination. |
Tier 2
- A. Glitazones, or thiazolidinediones:
Thiazolidinediones were often administered until 1990. Only pioglitazone is utilized, nevertheless, these days. It has also been connected to cases of bladder cancer, albeit the evidence for this was found to be insufficient. But be mindful of bladder cancer symptoms if you are using this medicine. Metformin can be administered along with glitazones, which improve insulin sensitivity. Their use has decreased because of the possibility of heart failure, bone fractures, etc.
| How it works | Acts on adipose tissue and decreases peripheral insulin resistance. |
| Effectiveness | Less effective – 0.5-1.4% point reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Less convenient. |
| Side effects | Water retention, edema, weight gain, eyesight problems, reduced sense of touch, chest pain and infections, allergic skin reactions. Rare: macular edema (an eye complication), heart problems, liver failure anemia, bone fractures. |
| Doses and timing | Pioglitazone: 15-30mg once daily. |
| Precaution(use cautiously or avoid) | Heart failure, hypersensitivity. Increased risk of becoming pregnant if you are practicing birth-control. Very 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). |
| Cost | 90 tablets $22-$24. |
- B. Agonists for GLP1:
Intestinal cells create a peptide called GLP1, or glucagon like peptide-1, which increases the effectiveness of insulin production in response to glucose. But the peptide’s half-life is brief. GLP1 agonists are medications that function similarly to GLP1, but they have a longer half-life, so they can keep enhancing insulin release in response to glucose. These are a new class of injectable medications that are recommended to those whose diabetes cannot be controlled with oral medicine. Exenatide and liraglutide are the more well-liked members. This kind of drug has a lower risk of causing hypoglycemia because its primary function is to encourage natural insulin secretion. These drugs also cause weight loss, making them a desirable treatment option for obese people.
| How it works | Increases insulin secretion after eating even before the blood glucose starts to rise. As this response is related to carbohydrate in the gut, the chance of getting hypoglycemia is low. Delays the emptying of the stomach which slows glucose absorption into the bloodstream Decreases glucagon secretion by the pancreas which prevents the liver to release stored sugar into the bloodstream. |
| Effectiveness | Less effective – 0.5 to 1% point reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Very convenient. |
| Side effects | Nausea, diarrhea, vomiting, headaches, dizziness, increased sweating, indigestion, constipation, loss of appetite. |
| Doses and timing | Liraglutide: 0.6-1.8 mg subcutaneously once daily Exenatide: 5mcg 12 hourly within 60 minutes of meal. |
| Precaution( use cautiously or avoid) | Avoid if personal or family history of medullary thyroid carcinoma. Pancreatitis Hypersensitivity. |
| Pregnancy category(FDA classification) | C |
| Cost | 1 vial $100. |
OTHER THERAPY
- A. Medicines similar to sulphonylureas (meglitinides/glidedes):
Despite not belonging to the sulphonylurea family, these work via the same mechanism. Unlike sulphonylureas, these start acting as soon as they are taken and only last for a short while. These are recommended to reduce blood glucose rises that occur after meals.Those with type 2 diabetes who are not able to regulate their blood sugar levels with tier 1, step 1 medications are administered these. These are appropriate for those who lead non-routine lives because they can take the medication with food at any time. Important examples of meglitinide derivatives are nateglinide and repaglinide.
| How it works | Promotes insulin secretion by acting on beta cells of pancreas. |
| Effectiveness | Less effective – 0.5 to 1.5% point reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Convenient. |
| Side effects | Low blood glucose, indigestion, skin rashes, headache, nasal congestion, joint aches, back pain, liver problems, stomach pain, nausea, diarrhea, constipation |
| Doses and timing | Repaglinide: 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) | Liver or kidney impairment, elderly patients. Should be avoided in case of allergy to this. Before taking this medication, talk to your doctor if you are allergic to any other drug. Tell your doctor of any prescription/non-prescription medicine that you might be taking as these may interact with this medication causing dangerous side-effects. Tell your doctor about any surgery that you might undergo – including dental surgery, before taking this medication. Also talk to your doctor about taking alcohol along with this medicine. |
| Pregnancy category(FDA classification) | C |
| Cost | 90 tablet $28 – $63. |
- B. DPP-4 inhibitors, or lipitins:
Newer anti-diabetic medications are called lipitins. For type 2 diabetics who do not respond to sulfonylureas and metformin, they are prescribed. They increase insulin secretion, but they don’t result in hypoglycemia because of a different mechanism. This family includes the well-known medications sitagliptin, vildagliptin, saxagliptin, and linagliptin. These might encourage losing weight.
| How it works | DPP-4 is an enzyme that breaks down certain proteins (called incretins) produced by intestine that promote insulin production. This drug inhibits this enzyme and allows incretins to act longer.It reduces blood glucose spikes after meals and increases insulin secretion. This drug also decreases appetite and is helpful in reducing obesity. |
| Effectiveness | Low effective – 0.5-0.8% points reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Very convenient. |
| Side effects | Headache,itchy skin, serious allergic reaction(rare). Stomach problems (nausea, diarrhea, and stomach pain), Flu-like symptoms (headache, runny nose, sore-throat). Increased risk of inflammation of pancreas (pancreatitis) – if you have a severe pain in upper abdomen along with nausea or vomiting, immediately call for medical help. |
| Doses and timing | Vildagliptin: 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 history of inflammation of pancreas (pancreatitis). |
| Pregnancy category(FDA classification) | N (Not classified). |
| Cost | 28 tablets $132 -$158. |
- C. Inhibitors of α-glucosidase:
Another name for these is starch blockers. For type 2 diabetics who have trouble regulating their blood glucose levels with other drugs after meals, these are administered post-meal. Because alpha-glucosidase enzymes break down carbohydrates, less glucose is created when they are inhibited. Alpha-glucosidase inhibitors such as miglitol and acarbose are available and can be administered in combination with sulphonylureas.
| How it works | Delays carbohydrate absorption in the gut by reducing the rate of conversion of carbohydrates to glucose |
| Effectiveness | Less effective – 0.5-0.8% points reduction in level of glucose bound to hemoglobin(A1C levels). |
| Convenience | Convenient. |
| Side effects | Flatulence, abdominal bloating, diarrhea. |
| Doses and timing | Acarbose: 50-300mg daily at 3 divided doses Miglitol: 25-100 mg 3 times daily. |
| Precaution( use cautiously or avoid) | Abnormal liver function tests. |
| Pregnancy category(FDA classification) | B |
| Cost | 90 tablets $37-$54. |
- D. Inhibitors of SGLT2:
Sodium-glucose co-transporter-2 is referred to as SGLT2. It is a protein that returns blood-derived glucose to the kidney. Anything that lowers this will cause glucose to be eliminated from the urine, and this is what this family of medications accomplishes. Type 2 diabetics who do not respond to metformin and insulin are prescribed to this group of anti-diabetic drugs, which includes dapagliflozin and canagliflozin. This group is a more recent entry to the market. They lower blood sugar levels, however their usage has been restricted due to the rise in UTI and genital tract infection rates.
| How it works | Inhibits SGLT2 and promotes excretion of glucose via urine. |
| Effectiveness | Less effective – 0.5 to 1% point reduction in level of glucose bound to hemoglobin (A1C levels). |
| Convenience | Convenient. |
| Side effects | Hypoglycemia, UTI, genital infection, dysuria. |
| Doses and timing | Dapagliflozin: 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 |
| Cost | 28 tablets $158 -$269. |
- Combination oral medications to prevent diabetes:
Combinations of oral anti-diabetic medications can increase their effectiveness. There are a few well-liked combos on the market. They are as follows:
- Glipizide with metformin combination:
This well-liked combo is typically utilized when sulfonylureas or metformin by themselves are unable to control hyperglycemia.
| How it works | Glipizide stimulates insulin secretion while metformin slows sugar absorption, stops conversion of stored sugar into blood sugar by the liver and helps body use the natural insulin more efficiently. This way the combination reduces blood glucose level together. |
| Effectiveness | Moderately effective. |
| Convenience | Very convenient. |
| Side effects | Allergic reaction, diarrhea, hypoglycemia, lactic acidosis (needs emergency medical attention). |
| Doses and timing | Should start with 1 tablet containing 2.5mg glipizide and 250mg metformin. |
| Precaution(use cautiously or avoid) | Renal impairment. Drinking alcohol or taking other medications. |
| Pregnancy category(FDA classification) | C |
| Cost | 100 tablets $79. |
- Combination of metformin, vildagliptin, and sitagliptin:
If β-cells are preserved, this combination is particularly successful in type-2 diabetes. Both blood sugar regulation and beta cell activity are improved by this combination more so than by metformin alone. It is also prescribed to patients for whom hypoglycemia (low blood sugar) poses a significant risk, or in cases where sulphonylurea is not tolerated or contraindicated.
| How it works | Increases insulin release Decreases endogenous glucose production. |
| Effectiveness | Moderately effective. |
| Convenience | Very Convenient. |
| Side effects | Mild: Headache, stomach upset, nausea, vomiting, diarrhea, dermatitis, dizziness (worse with alcohol intake) is common on starting the treatment. Severe: Lactic acidosis (which needs emergency attention) can develop later during treatment. Severe inflammation of pancreas can occur which can be fatal. Discuss with your doctor immediately if you develop severe or persistent stomach or back pains which may be accompanied by nausea and vomiting. |
| Doses and timing | Dose need to be individualized. Usually administered twice daily with meal. |
| Precaution( use cautiously or avoid) | Liver disease, renal impairment, older than 80 years, stroke or heart attack, surgery or lab procedures. |
| Pregnancy category(FDA classification) | B |
| Cost | 60 tablet $144-$177. |
- Combination of glimepride and pioglitazone:
There are tablets available that contain pioglitazone (15/30 mg) and glimepride (2/4 mg). Although pioglitazone side effects make it less popular, it can be useful for many patients.
| How it works | Increases insulin secretion Decreases peripheral insulin resistance. |
| Effectiveness | Moderately effective. |
| Convenience | Convenient. |
| Side effects | Hypoglycemia, edema, bone fracture, drowsiness, dizziness, blurred vision, or light-headedness, increased risk for heart disease and bladder cancer, severe skin reaction (Steven-Johnson syndrome/toxic epidermal necrolysis) which can be serious and cause death, serious and sometimes fatal liver problems. |
| Doses and timing | Initially, 1 tablet once daily and then titrate gradually. |
| Precaution (use cautiously or avoid) | Heart failure, bone disease, elderly, children, bladder cancer, high blood acid levels (ketoacidosis), type 1 diabetes. |
| Pregnancy category(FDA classification) | C |
| Cost | 15 tablets $4-$5. |
- *Pregnancy Categories on FDA
Five categories have been created by the FDA to identify whether a medicine has the potential to cause birth abnormalities if used while pregnant. The risk to benefit ratio—that is, if the advantages outweigh the risks or vice versa—and the quality of the documentation determine which category these fall into. They don’t account for the possibility of pharmaceuticals or their metabolites being in breast milk. Pregnancy classifications include:
- Category A
There is no evidence of risk to the fetus in the first trimester of pregnancy, and adequate and carefully controlled studies have not shown any risk.
- Category B
Studies on animal reproduction have not shown any danger to the developing foetus, and sufficient, well monitored research on pregnant women is lacking.
- Category C
Although there are insufficient and poorly controlled human trials and the medicine has been proven to have a negative effect on the fetus in animal reproduction research, pregnant women may still benefit from using it despite the dangers.
- Category D
Based on adverse reaction data from human studies or marketing experience, there is positive evidence of human fetal risk; nevertheless, possible benefits may outweigh any risks in the case of pregnant women using the medicine.
- Category X
The dangers associated with using the medication in pregnant women obviously outweigh any potential benefits, as studies on people or animals have shown fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from experimental or marketing experience.
- Category N
The medicine is not classified by the FDA.