Antidiabetic drugs are those drugs that reduce blood sugar levels by releasing insulin or overcoming insulin resistance. Antidiabetic drugs have been classified into two forms: injectable and oral antidiabetic drugs (OHA – Oral Hypoglycemic Agents) - Injectable Diabetes Medications Injections are not the first choice drug for diabetes. They are last-line medication options if your diabetes is getting uncontrolled. You can be given the following injections – *Insulin analogues *Incretins based drugs such as GLP-1 analogs (Exenatide and Liraglutide) -Oral Hypoglycemic Drugs (or Antidiabetic Agents) The major drawback of insulin analogues is that it is given by injection. That’s why oral hypoglycaemic medicines are preferable and commonly used in type-2 diabetes mellitus treatment. Oral hypoglycemic agents are quite effective to control your high blood glucose levels. It only works on type 2 diabetes mellitus. Currently, there are 4 ways/groups of oral antidiabetic medicines to reduce high blood sugar levels – *Insulin sensitizers *Insulin secretagogues *Decrease intestinal absorption of glucose *Excretion of glucose from urine Oral antidiabetic medications have been classified into 7 classes, such as – 1. Biguanides 2. Thiazolidinediones 3. Sulfonylureas 4. Meglitinides 5. DPP-4 inhibitors 6. Alpha-glucosidase inhibitors 7. SGLT2 Inhibitors This article will explore various antidiabetic drug classifications, their mechanism of action, uses, side effects and dosage. Moreover, we will understand what medicines are preferable and suitable for treating diabetes mellitus.

1. Antidiabetic Drug Classification and
Mechanism of Action: algorithm for
management of diabetes mellitus
Posted By SUMIT SHARMA
Contents
● Introduction
● What are antidiabetic drugs?
● What are the classifications of antidiabetic drugs with examples?
Injectable Diabetes Medications
Oral Hypoglycemic Drugs (or Antidiabetic Agents)
● Which drugs are Biguanides?

2. Mechanism of action of metformin
Side effects of metformin
Dosage of metformin
● What drugs are Sulphonylureas? What can be the role of Sulphonylureas in treatment of diabetes?
Sulfonylureas mechanism of action
Side effect of Sulphonylureas
Dosage of Sulphonylureas
● What are examples of meglitinide analogues? Why meglitinides are better than sulfonylureas?
Meglitinide’s mechanism of action
Benefits of Meglitinides
Dosage of Meglitinides
● What is the mechanism of thiazolidinediones? Is pioglitazone safe to take for diabetes?
Pioglitazone mechanism of action
Pioglitazone side effects and contraindications
Pioglitazone benefits
● Which drugs are DPP-4 inhibitors? How do DPP-4 inhibitors work?

3. DPP-4 inhibitor’s mechanism of action
DPP-4 inhibitors brand names
● What are currently used alpha-glucosidase inhibitors? What is the clinical role of these drugs in
diabetes mellitus?
Alpha-glucosidase inhibitor’s mechanism of action
Alpha-glucosidase inhibitor’s side effects
Acarbose and voglibose dosage
● What are the most common SGLT2 inhibitors? How do SGLT2 inhibitors work?
SGLT2 inhibitor’s mechanism of action
SGLT2 inhibitor’s side effects
● What are insulin analogues? What are the different types of insulin names?
1. Short-acting insulin
2. Ultra short-acting insulin
3. Intermediate-acting Insulin
4. Long-acting insulin
5. Ultra-long acting insulin

4. 6. Premixed Insulin
Combination of intermediate and ultra-short-acting insulin
Combination of intermediate and short-acting insulin
Combination of ultra-short and ultra-long-acting insulin
● What is the role of liraglutide and exenatide in diabetes mellitus?
● What is the pharmacological management of diabetes mellitus?
STEP 1 – Mono-therapy
STEP 2 – Dual therapy
STEP 3 – Triple Therapy
STEP 4 – Injectable with combinations
● Conclusion
● FAQ
Q 1. What is the first drug of choice for diabetes?
Q 2. Which antidiabetic drug class lead to glycosuria?
Q 3. What is the new drug for diabetes?
Q 4. Is repaglinide safe for kidneys?

5. Q 5. Is linagliptin safe for kidneys?
Introduction
You must have a diabetic person in your family or relatives. They would be taking
different diabetes medications. Today, we will get to know the complete
antidiabetic drug classification.
Lifestyle modifications (such as diet control and exercise) are the gold standard for
treating diabetes.
We should add the best diabetic diet plan, such as low glycemic index foods, low
glycemic load foods, high protein food, proper fluid intake, etc.
Suppose the lifestyle changes do not work and your blood sugar is still high. In that
case, antidiabetic drugs should be added to your diabetes treatment.
It does not mean you should stop exercising and not eating healthy foods. You have
to add on medicine with healthy lifestyle activities.
This article will explore various antidiabetic drug classifications, their mechanism
of action, uses, side effects and dosage.
Moreover, we will understand what medicines are preferable and suitable for
treating diabetes mellitus.
Let the article be started.
What are antidiabetic drugs?
Antidiabetic drugs are those drugs that reduce blood sugar levels by releasing
insulin or overcoming insulin resistance. It makes your blood sugar level in normal
ranges –
● FBS = 99 mg/dl or below

6. ● PPBS = 140 mg/dl or below
● RBS = below 200 mg/dl
● HbA1C = <5.7%
These drugs resolve diabetic symptoms by decreasing blood sugar levels, such as –
● Decrease tiredness
● Control excessive urination
● Control excessive eating
● Control intense thirst
● Prevent weight loss
● Stop dehydration
Antidiabetic drugs also prevent diabetic complications such as
● Macrovascular complications– Reduce the risk of Cerebrovascular Disease
(CVD), Coronary artery disease (CAD), Peripheral vascular disease (PVD),
and Renovascular Disease (RVD)
● Microvascular complications – Reduce the risk of Diabetic neuropathy,
Diabetic nephropathy, and Diabetic retinopathy

7. What are the classifications of antidiabetic drugs with
examples?
Antidiabetic drugs have been classified into two forms: injectable and oral
antidiabetic drugs (OHA – Oral Hypoglycemic Agents)
Injectable Diabetes Medications
Injections are not the first choice drug for diabetes. They are last-line medication
options if your diabetes is getting uncontrolled. You can be given the following
injections –
● Insulin analogues
● Incretins based drugs such as GLP-1 analogs (Exenatide and Liraglutide)
Oral Hypoglycemic Drugs (or Antidiabetic Agents)
The major drawback of insulin analogues is that it is given by injection. That’s why
oral hypoglycaemic medicines are preferable and commonly used in type-2
diabetes mellitus treatment.
Oral hypoglycemic agents are quite effective to control your high blood glucose
levels. It only works on type 2 diabetes mellitus.
Currently, there are 4 ways/groups of oral antidiabetic medicines to reduce high
blood sugar levels –
● Insulin sensitizers
● Insulin secretagogues

8. ● Decrease intestinal absorption of glucose
● Excretion of glucose from urine
Oral antidiabetic medications have been classified into 7 classes, such as –
1. Biguanides
2. Thiazolidinediones
3. Sulfonylureas
4. Meglitinides
5. DPP-4 inhibitors
6. Alpha-glucosidase inhibitors
7. SGLT2 Inhibitors
Groups Classes Examples of medicines
Insulin sensitizers
Biguanides Metformin
Thiazolidinediones Pioglitazone
Sulfonylureas Glipizide, Glimepiride,
Glyclazide,

9. Insulin secretagogues
Glyburide
Meglitinides Repaglinide, Nateglinide
DPP-4 inhibitors Sitagliptin,
Saxagliptin,
Linagliptin,
Vildagliptin
Decrease intestinal
absorption of glucose
Alpha-glucosidase
inhibitors
Acarbose, Voglibose
Miglitol
Excretion of glucose
from urine
SGLT2 Inhibitors Dapagliflozin,
Empagliflozin,
Canagliflozin

10. Which drugs are Biguanides?
Metformin is a drug that belongs to the biguanide category.
Everyone knows this drug because metformin tablet is the most commonly
prescribed medicine for type 2 diabetes mellitus (T2DM). This is the initial drug
where diabetes treatment should be started.
It is considered a first-line drug in treating type 2 diabetes mellitus.
Let’s know the pharmacology of metformin drug –
Mechanism of action of metformin
Metformin drug works in three ways –

11. ● Decrease glucose absorption from the intestine
Metformin reduces gluconeogenesis. This means it decreases the absorption or
formation of a new glucose molecule (e.g., protein) from the intestine.
● Decrease glucose production in the liver
Metformin reduces hepatic glycogenolysis. This means that it decreases the
breakdown of glycogen, which converts into glucose and decreases glucose
transport from the liver to the blood.
● Increase insulin sensitivity and glucose uptake in cells
Metformin helps to reduce insulin resistance. This drug activates Insulin, which
helps to transport glucose molecules from blood to cells.

12. Side effects of metformin
The main side effects of metformin are related to the gastrointestinal tract, which is
very common. This medicine can cause diarrhoea, bloating, flatulence, nausea, etc.
You might have dangerous side effects if you are using metformin. Lactic acidosis
has been reported due to the use of excessive metformin doses.
This side effect could be fatal if your kidney and liver are compromised.
Metformin can also cause vitamin B12 deficiency. You may need to add vitamin
B12 supplements along with metformin.
Dosage of metformin
The maximum dosage of metformin per day is 2000 mg. It would be best if you do
not go beyond this dose.
Initially, your diabetes treatment should be started at 500 mg twice daily. It could
be increased up to 1000 mg twice if diabetes is uncontrolled.
This drug can be combined with other antidiabetic classes like sulphonylureas,
DPP-4 inhibitors, SGLT2 inhibitors, Meglitinides, thiazolidinediones, and
alpha-glucosidase inhibitors.
You can take metformin just after having your meal.

14. What drugs are Sulphonylureas? What can be the role of
Sulphonylureas in treatment of diabetes?
You must have heard the names of diabetic medicines which begin with “Gli”, like
Glimepride, Gliclazide, Glibenclamide, and Glipizide.

15. These drugs are second-generation of sulphonylureas. The first generation of
sulphonylureas, such as tolbutamide and chlorpropamide, are rarely used.
The sulphonylureas have a crucial role in the treatment of T2DM by releasing
insulin from the pancreas.
These drugs are also known as Insulin Secretagogous.
Suppose you are intolerant of metformin. In that case, you can use sulphonylureas
alone.
It can also be used in combination with metformin.
Sulfonylureas mechanism of action
When you take any sulphonylureas drug. They go to your pancreas and stimulate
beta cells.
Here, it blocks the ATP-sensitive potassium (K+) channel. Due to this, a high
concentration of potassium in your beta cells stimulates the calcium channel.
As soon as the calcium channel opens, it starts letting the influx of calcium ions.
This increased influx of calcium ions penetrates the large, dense core vesicles
where insulin is stored.
In this process of depolarisation, exocytosis takes place, and insulin is secreted.
Overall, sulphonylureas help to secrete insulin. That’s why it is called Insulin
Secretagogues.
After releasing insulin, it goes to the liver by the hepatic portal vein. Eventually,
insulin reaches the central blood circulation.
Here, insulin goes to cells and binds to the Tyrosine Kinase receptor. After that, it
lets the glucose come inside cells by GLUT-4 transporters.

16. Side effect of Sulphonylureas
You may have hypoglycaemia and weight gain-like side effects during
sulphonylureas therapy.
Hypoglycemia was very common in first-generation sulphonylureas like
tolbutamide and chlorpropamide.
The risk of hypoglycaemia is lower in newer sulphonylureas drugs like glimeride,
gliclazide, etc.
Dosage of Sulphonylureas
It is usually recommended to start with a low dose, such as glibenclamide 2.5 mg,
glimepiride 2 mg, gliclazide 30 mg, etc.

17. The dose of sulphonylureas can be increased every two weeks if your glycemic
pattern is not controlled well.
It would be best if you take sulphonylureas 30 min before each meal once or twice
a day as needed.

18. What are examples of meglitinide analogues? Why
meglitinides are better than sulfonylureas?
Meglitinides are also effective oral hypoglycaemic drugs. There are two medicines
in this category, such as repaglinide and nateglinide.

19. Repaglinide is considered a superior and preferable drug because of better
glycemic control. It effectively controls elevated post-prandial blood sugar (PPBS)
in T2DM.
These drugs have a good reduction in HbA1C, around 0.2 to 1.5%.
According to current guidelines, meglitinides are not recommended as part of an
oral diabetes treatment regimen. Still, they may be used instead of sulfonylureas in
selected patients.
Meglitinides can be used if someone has an allergy or is intolerant of
sulphonylureas. It can also be used in kidney disease patients who have T2DM.
Meglitinide’s mechanism of action
Meglitidines have similar mechanisms to Sulphonylureas. They block the
potassium channel and secrete insulin. These medicines are also known as Insulin
Secretagogues.
Benefits of Meglitinides
● Repaglinide is the safest and most well-tolerated drug in chronic kidney
disease.
● A safe and effective drug in an elderly diabetic patient
● Well-controlled post-prandial blood glucose (PPBG) level
● Quickly absorbed in the bloodstream
● Fast onset of action

20. ● Lower risk of hypoglycaemia
Dosage of Meglitinides
This class of medicines should be taken 10 minutes before each meal to control
your PPBS level.
The recommended dose range of repaglinide is 0.5 mg to 4 mg. It can be increased
up to 16 mg as needed.
What is the mechanism of thiazolidinediones? Is
pioglitazone safe to take for diabetes?
Thiazolidinediones (TZDs) are also known as “Glitazones”. Glitazones are the
second or third-line treatment option for type 2 diabetes mellitus. It includes
rosiglitazone and pioglitazone.
In 2010, Rosiglitazone was banned in many countries due to increasing
life-threatening risks such as myocardial infarction, CHF, stroke and death.
These drugs have been completely withdrawn from European countries like
Germany and France due to increased risk of bladder cancer and cardiovascular
problems.
Currently, only pioglitazone is available in some countries like India. It is used as a
mono-therapy in case of intolerance of metformin.
If diabetes is uncontrolled, then combinations can be used of pioglitazone with
other antidiabetic drugs –

21. ● Dual therapy (Pioglitazone + Metformin, or Sulphonylureas, or DPP-4
inhibitors)
● Triple therapy (Metformin + Pioglitazone + SGLT2 inhibitors) or
(Metformin + Sulfonylurea + Pioglitazone)
Pioglitazone mechanism of action
Pioglitazone drug works on the nuclear receptor, which stimulates PPAR- γ
(peroxisome proliferator-activated receptor gamma).
PPAR- γ receptors are mainly present in fat cells. It alters the transcription of
several genes and enhances GLUT4 expression, improving glucose entry into fat
cells.
Overall, it reduces insulin resistance by increasing insulin sensitivity.

22. Pioglitazone side effects and contraindications
The most common side effects of pioglitazone are fluid retention and weight gain.
You may notice swelling in your ankles if you are on pioglitazone.
You should avoid pioglitazone if you have a history of heart disease because it may
worsen the condition of CHF (Congestive Heart Failure).
The liver dysfunctions have been reported by pioglitazone. So, you may require
monitoring of LFT (Liver function test).
According to a study, pioglitazone is also associated with an increased risk of bone
fractures, especially in older women.
Pioglitazone has lack of safety data in pregnancy. So, you should avoid this drug
during pregnancy.

23. Pioglitazone benefits
Pioglitazone effectively controls elevated blood sugar levels if there is a clear case
of insulin resistance. Let’s know it’s crucial benefits –
● Well-tolerated drug in T2DM
● Decrease TG (triglyceride) level
● Increase HDL level
● Less hypoglycaemic episodes
Which drugs are DPP-4 inhibitors? How do DPP-4
inhibitors work?
DPP-4 inhibitors are considered newer antidiabetic drugs. These drugs are also
called “Gliptins” because these drugs end with the “gliptins” word. For examples –
● Sitagliptin
● Saxagliptin
● Linagliptin
● Vildagliptin
● Teneligliptin

24. If metformin is intolerant, your doctor can start DPP4 inhibitors as a mono-therapy
(single drug therapy).
In case diabetes is uncontrolled, then combinations can be used of DPP-4 inhibitors
with other antidiabetic drugs –
● Dual therapy (DPP4 inhibitors + metformin, or sulphonylureas, or
pioglitazone)
● Triple therapy (Metformin + Sulfonylurea + DPP4 inhibitors)
DPP-4 inhibitor’s mechanism of action
Taking food stimulates incretins like GIP (gastric inhibitory polypeptide) and
GLP-1 (glucagon‐like peptide‐1).
These incretins go to the pancreas and get the insulin secreted.
But, you might have a problem when DPP-4 (Dipeptidyl-peptidase 4) enzymes are
released. These DPP-4 enzymes inhibit the release of incretins and stop insulin
secretion.
That’s why researchers have made a molecule that inhibits the DPP-4 enzyme.
They launched DPP-4 inhibitors. These drugs are also insulin secretagogous.
DPP-4 inhibitors are those drugs that inhibit Dipeptidyl-peptidase 4 enzyme and
release incretins like GIP and GLP-1. These incretins help to release insulin to
control high blood glucose levels.

25. DPP-4 inhibitors brand names
There are some popular brand names for DPP-4 inhibitor drugs –
● Sitagliptin (Januvia)
● Saxagliptin (Onglyza)
● Linagliptin (Trajenta)
● Vildagliptin (Galvus)

28. Gliptins are commonly used in fixed-dose combinations with metformin drugs like
–
● Janumet (Sitagliptin 50 mg and metformin hydrochloride 500 mg/1 gm)
● Kombiglyze XR (saxagliptin 5 mg and metformin HCl 500 mg/1 gm
extended-release)
● Trajenta Duo (Linagliptin 2.5 mg and metformin hydrochloride 500 mg)
● Galvus Met (Vildagliptin and metformin HCL 500 mg/1 gm)

30. What are currently used alpha-glucosidase inhibitors?
What is the clinical role of these drugs in diabetes
mellitus?
Currently, Acarbose and Voglibose are the classical alpha-glucosidase inhibitors
used to treat T2DM.
Suppose you are newly diagnosed with type 2 diabetes mellitus. And, your
post-prandial blood glucose is not controlled with diet or exercise. In that case, this
drug can also be used as a first-line drug.
It can also be used with metformin and other antidiabetic drugs.
Alpha-glucosidase inhibitor’s mechanism of action

31. Typically, Alpha-glucosidase is an enzyme in our intestinal brush border.
This enzyme is released from the small intestine when we eat carbohydrates. It
helps to break down carbohydrates in the simplest form, like glucose.
In diabetes conditions, this alpha-glucosidase enzyme increases the process of
glucose digestion and absorption. This is not good in hyperglycaemic states.
Here, alpha-glucosidase inhibitors (such as acarbose and voglibose) inhibit the
alpha-glucosidase enzyme. It delays the process of digestion and absorption of
carbohydrates.
Eventually, these drugs decrease glucose absorption in the bloodstream and reduce
blood glucose levels.
Alpha-glucosidase inhibitor’s side effects

32. The unabsorbed carbohydrates may cause abdominal bloating, cramping, increased
flatulence, or diarrhoea.
You may have these side effects if you are on voglibose or acarbose.
Acarbose and voglibose dosage
You may take acarbose 50 to 100 mg or voglibose 0.2 to 0.3 mg thrice a day before
the beginning of each meal.
What are the most common SGLT2 inhibitors? How do
SGLT2 inhibitors work?
SGLT2 inhibitors are newer antidiabetic drugs that help to treat type 2 diabetes
mellitus.
They are also known as Gliflozins because these medicines end with “gliflozin”,
word such as

33. ● Dapagliflozin
● Empagliflozin
● Canagliflozin
This drug class can be used as a mono-therapy if metformin is intolerant or
contraindicated.
In case of uncontrolled glycemic pattern, it should be started in combinations as a –
● Dual therapy (SGLT2 inhibitors + metformin, or sulphonylureas)
● Triple therapy (Metformin + Sulfonylurea + SGLT2 inhibitors) or
(Metformin + Pioglitazone + SGLT2 inhibitors)
SGLT2 inhibitor’s mechanism of action
SGLT2 inhibitors have a novel and unique mechanism of action.
In a healthy person, there are SGLT-2 co-transporters or pumps in their kidney’s
nephron. The full form of SGLT is Sodium Glucose Co-Transporter.
These transporters act as symporters that reabsorb sodium and glucose in your
blood during urine formation.
In diabetes mellitus, re-absorption of glucose and sodium is not good, which may
worsen your diabetic condition.
Here, SGLT2 inhibitors inhibit the SGLT2 co-transporters that excrete the sodium
and glucose through urine.
Due to this unique mechanism, it significantly reduces blood glucose levels.

34. SGLT2 inhibitor’s side effects
You may have the following side effects during gliflozins therapy –
● Frequent urination
● Dehydration and hypotension
● Weight loss
● Hypoglycemia
● Excessive thirst and frequent urination
● Risk of foot amputations

35. ● Risk of bone fractures

36. What are insulin analogues? What are the different types
of insulin names?
Insulin shots are the last-line medication option to control high blood sugar levels.
Insulin injections are used to management of Type 1 (T1DM) and Type 2 Diabetes
Mellitus (T2DM).
If you don’t have enough natural insulin, synthetic insulin should be given to you.

37. This synthetic insulin is called Insulin analogue.
Insulin analogue imitates the body’s standard insulin release patterns.
Insulin analogue injections are made using the pancreas of pigs (pork) and cows
(beef). They can also be prepared by recombinant DNA technology.
In recombinant DNA technology, scientists use human pancreatic genes in E. coli
(Escherichia coli) bacteria. They make insulin analogue.
There are different insulin types for diabetes. Some insulin analogues control the
peak of glucose concentration; that insulin is called Bolus Insulin.
Bolus insulin is fast-acting insulin that immediately releases in your bloodstream
and controls high blood sugar levels. They are given immediately just before your
meal.
Conversely, those insulin analogues that maintain your blood sugar level for a long
time are called Basal Insulin.
Basal Insulin is slow-acting or long-acting insulin. They release slowly in your
bloodstream. When you take basal insulin, your blood glucose level remains steady
throughout the day and night.
Let’s know the different types of insulin preparations –
1. Short-acting insulin
Regular Insulin or soluble Insulin is an example of short-acting insulin. This is a
type of Bolus Insulin. This insulin preparation is in Human Actrapid Injection at 40
IU/ml.
If you see the cartridge or vial of short-acting insulin, it would be a clear
appearance.
The onset of action is 30 mins, and the duration is 6 to 8 hours of regular insulin.

38. This means that regular insulin takes 30 mins to reach your blood circulation after
subcutaneous injection and remains in your blood for 6 to 8 hours.
It shows the maximum effect (peak) in 2 to 3 hours.
You need to take Regular Insulin 30 minutes before a meal.
This is the limitation of Short-acting Insulin. It is not always possible to inject
insulin before 30-minute meal. It reduces patient compliance and does not
significantly reduce PPBG levels.
Other insulin preparations have been designed to overcome this problem, such as
ultra-short, intermediate, long, and ultra-long-acting Insulin Injections.
2. Ultra short-acting insulin
The most common type of insulin injection is ultra-short-acting insulin. This
injection reduces the limitation of Regular Insulin (or Short-acting insulin).
It is a clear appearance.
It quickly absorbs in your bloodstream within 5 to 15 mins (onset of action). The
duration of action is 2 to 4 hours.
You need to prepare your meal and take a shot of ultra-short-acting insulin. It is an
effective bolus insulin because it significantly reduces elevated blood glucose level
spikes or PPBG.
Examples of ultra-short-acting Insulin are Lispro, Aspart and Glulisine. You might
have seen –
● Insulin Lispro in Humalog 100.
● Insulin Aspart in NovoRapid and NovoLog
● Insulin Glulisine in Apidra Solostar

40. 3. Intermediate-acting Insulin
Intermediate-acting insulin is a Basal Insulin that keeps your blood sugar level
stable when fasting, such as while you sleep.
An example of intermediate Insulin is Isophane. It is also known as NPH (Neutral
Protamine Hagedorn) Insulin.
Isophane is mainly used to make premixed insulin. It is compatible to mix with
short or rapid short-acting insulin.
You can easily identify this type of insulin. When you see the vial or cartridge of
intermediate-acting insulin, it would have a cloudy appearance.
The onset of action is 60 to 90 min. It will reach a maximum concentration or peak
in 8 to 10 hours. It will remain in your body for 20 to 24 hours.

41. You might need to inject Isophane insulin subcutaneously (s.c.) once or twice daily.
Isophane or NPH is available in the market with Huminsulin and Humulin N brand
names.
4. Long-acting insulin
It is a long-acting basal insulin analogue. Example of long-acting Insulin is Insulin
Detemir and Insulin Glargine.
Insulin glargine is very popular with the brand names Lantus and Basalog, and
insulin detemir is available in the Levemir brand name.
These long-acting insulin injections maintain your blood sugar level throughout the
night. These injections start to work after 2 hrs.
The duration of action is 24 hrs. It can be injected at any time, but you should take
it at the same time every day.
The long-acting Insulin (Lantus) is generally recommended at bedtime.

42. 5. Ultra-long acting insulin
Insulin degludec is an ultra-long-acting basal insulin analogue that prevents strong
fluctuation of blood sugar levels. It is very popular with the brand name of Tresiba.
The duration of action of Tresiba is more than 24 hrs and lasts up to 42 hours.
You can inject Tresiba subcutaneously once daily at any time of day.

44. 6. Premixed Insulin
Premixed insulin is a combination of two different types of insulin. It is a fixed
composition of rapid or short-acting and intermediate- or long-acting insulin.
Intermediate-acting insulin is commonly used with ultra-short and short-acting
insulin to prepare premixed insulin.
This is a combination of bolus and basal insulin analogue.
Premixed insulin formulations are selected according to patient characteristics and
based on glycemic patterns to manage diabetes mellitus.
These premixed insulin injections can be injected once, twice or thrice as per
patient requirement.
Premixed insulin is available in different combinations –
Combination of intermediate and ultra-short-acting insulin
Despite using intermediate insulin, they have a quicker onset of action. So, you
need to inject these injections before 15 15-minute meal.
The examples are –
● Humalog Mix 25 (Insulin Lispro 25% + Insulin Lispro Protamine 75%)
● Humalog Mix 50 (Insulin Lispro 50% + Insulin Lispro Protamine 50%)
● NovoMix 30 (30% insulin aspart and 70% insulin aspart protamine)

47. Combination of intermediate and short-acting insulin

48. You can see this biphasic human insulin in –
● Wosulin (30% soluble insulin and 70% isophane insulin)
● Human Mixtard 70/30 (70% Insulin Isophane/NPH 70% + 30% Human
Insulin/Soluble Insulin)
Here, soluble/NPH insulin is short-acting, and Isophane is intermediate.
It would be best to take this injection 30 minutes before the meal.
Combination of ultra-short and ultra-long-acting insulin
Ryzodec is a classic example of this combination. It significantly controls both
fasting and post-prandial blood sugar levels.
Ryzodec contains 70% insulin degludec and 30% insulin aspart.
Here, Insulin degludec is ultra-long-acting insulin. While Insulin aspart is an
ultra-short-acting insulin.
It is given once a day immediately before a meal.
What is the role of liraglutide and exenatide in diabetes
mellitus?
Liraglutide and exenatide are incretins-based drugs. They are also known as newer
antidiabetic drugs. They were introduced in 2005.

49. These incretin-based drugs are also the last step medication option to control high
blood sugar levels.
Although, the mechanism of incretin-based drugs seems to be DPP-4 inhibitors.
But there are some differences in mechanism. DPP-4 inhibitors are incretin
enhancers. They indirectly release incretins by inhibiting the DPP-4 enzyme and
letting the incretin go to the pancreas.
On the contrary, liraglutide and exenatide are synthetic incretins such as GLP-1
(Glucagon-like peptide-1). These drugs are also called GLP-1 agonists.
These GLP -1 agonist drugs directly release insulin to pancreatic beta cells.
GLP -1 agonist drugs are available in the market in injection form in brands of
● Liruglutide – Victoza and Saxenda injection
● Exenatide – Byetta injection
It can be used in combination with oral triple therapy.
● Metformin + Sulfonylurea + GLP-1 agonist
● Metformin + SGLT2 inhibitors + GLP1 agonist
● Sulfonylurea + SGLT2 inhibitors + GLP1 agonist
● SGLT2 inhibitors + GLP1 agonist
DPP4 inhibitors and GLP1 agonist combinations are not recommended in T2DM
due to a similar mechanism.

50. What is the pharmacological management of diabetes
mellitus?
There is a proper way or rules to manage any disease. This treatment plan is called
algorithm.
Here, we will know the algorithm for managing T1DM and T2DM.
If you have newly detected diabetes, then the treatment plan should be started in
the following ways –
Management of T1DM (Type 1 Diabetes Mellitus)
If a patient has T1DM, there would be few options. It should be started with diet
control, exercise and Insulin injections.
Management of T2DM (Type 2 Diabetes Mellitus)
If you have T2DM and your blood sugar level is not controlled by diet
modification and exercise.
STEP 1 – Mono-therapy
The primary goal of mono-therapy is to HbA1c <7.5%.
Metformin is an initial therapy (or First-line drug) for treating T2DM. You should
be on –
Diet control + exercise + Metformin tablet
If Metformin is contraindicated or intolerant. In that case, the following drugs
should be added –
● Sulphonylureas

51. ● Or DPP4 inhibitors “gliptins,” e.g. Sitagliptin, linagliptin, etc.
● Or SGLT2 inhibitors “gliflozins,” e.g. dapagliflozin, empagliflozin and
canagliflozin
● Or Pioglitazone
STEP 2 – Dual therapy
Your doctor may start dual therapy if HbA1C > 7.5%.
For non-obese patient
● Metformin + Sulfonylurea, or
● Sulfonylurea + Pioglitazone (If metformin is contraindicated or intolerant)
For obese patient
● Metformin + DPP4 inhibitors or SGLT2 inhibitors or Pioglitazone
If Metformin is contraindicated or intolerant. In that case, the following drugs
should be added –
● Sulfonylurea + DDP4 inhibitors
● Or Sulfonylurea + Pioglitazone
● Or DPP4 inhibitors + Pioglitazone
● Or SGLT2 inhibitors + Sulphonylureas

52. STEP 3 – Triple Therapy
You may require triple therapy if HbA1C > 9%. It can be started in combination
with metformin and other antidiabetic drugs –
● Metformin + Sulfonylurea + SGLT2 inhibitors
● Or, Metformin + Sulfonylurea + DPP4 inhibitors
● Or, Metformin + Sulfonylurea + Pioglitazone
● Or, Metformin + Pioglitazone + SGLT2 inhibitors
If metformin is intolerant or Contraindicated, then the patient will require
injectable therapy (Step 4)
STEP 4 – Injectable with combinations
There are three options in combination; it can be started as per your need and based
on glycemic pattern –
Option 1 – Oral Triple therapy with GLP1
● Metformin + Sulfonylurea + GLP-1
● Metformin + SGLT2 inhibitors + GLP1
● Sulfonylurea + SGLT2 inhibitors + GLP1
● SGLT2 inhibitors + GLP1

53. Note – Do not use DPP4 and GLP1 in combination.
Option 2 – Oral Triple Therapy with Insulin
● Metformin + Sulfonylurea + Insulin
● Metformin + SGLT2 inhibitors + Insulin
● Metformin + DPP4 inhibitors + Insulin
● Sulfonylurea + DPP4 inhibitors + Insulin
● Sulfonylurea + SGLT2 inhibitors + Insulin
● SGLT2i + DPP4 inhibitors + Insulin
● SGLT2i + Insulin
Option 3 – GLP1 and Insulin
Conclusion
Life does not end with diabetes; it can be managed by lifestyle modification.
The best way to manage diabetes is to educate the patient. Patients should be aware
of their diet and exercise. They should know what antidiabetic medicines have
been prescribed.
There are proper steps (or algorithms) of antidiabetic medicines to manage diabetes
mellitus.

54. A good doctor always follows the algorithm for the treatment of diabetes mellitus.
This post has discussed the antidiabetic drug classification, mechanism, uses,
dosage, and side effects.
These antidiabetic medicines play a significant role in controlling your blood sugar
level.
If you found this post informative, please share it on social media.
References –
1. D. Tripathi, Essentials of medical pharmacology, 7th Edition. Jaypee
Brothers Medical Publishers (P) Ltd; 2013. Chapter – 19, Insulin, oral
hypoglycemic agents and glucagon, Page – 258.
2. Diabetes education online, university of California. https://dtc.ucsf.edu/
3. Electronic medicines compendium (EMC)
https://www.medicines.org.uk/emc
4. National clinical guidelines for management of diabetes mellitus, 2010, first
edition.
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995498/
6. https://www.medicines.org.uk/emc/product/594/smpc

55. 7. https://dtc.ucsf.edu/types-of-diabetes/type2/treatment-of-type-2-diabetes/me
dications-and-therapies/type-2-non-insulin-therapies/insulin-sensitizers/
8. https://pubmed.ncbi.nlm.nih.gov/11921433/
FAQ
Q 1. What is the first drug of choice for diabetes?
Metformin is the first drug of choice for type 2 diabetes mellitus (T2DM). This
medicine should be started initially in newly detected diabetes patients.
Q 2. Which antidiabetic drug class lead to glycosuria?
The SGLT2 inhibitors (dapagliflozin, empagliflozin and canagliflozin) have a
unique mechanism to excrete glucose from urine. Due to this, you may have a
glycosuria effect.
Q 3. What is the new drug for diabetes?
GLP agonists (Liraglutide and exenatide), DPP4 inhibitors (gliptins), and SGLT2
inhibitors (Gliflozins) are considered newer drugs for diabetes mellitus. Still, the
FDA approved Baxagliflozin (SGLT2 inhibitors) on Jan 23, 2023.
Q 4. Is repaglinide safe for kidneys?
Yes. Repaglinide is an absolutely safe and well-tolerated drug in kidney disease
patients with type 2 diabetes mellitus.
Q 5. Is linagliptin safe for kidneys?

56. Linagliptin is mainly (90%) excreted via faeces by hepatobiliary route. It is
excreted in small quantities (1 to 6%) through urine. So, Linagliptin (Trajenta) is
safe for kidney disease patients.
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