Endo - Drugs used in the management of Diabetes Mellitus

Question 1

How does an increase in glucose level stimulate insulin release?

Answer 1

Increased intracellular glucose leads to increased production of ATP, and an increase in the ATP/ADP ratio (1); the increased ATP/ADP ratio leads to closure of the potassium channels and depolarization of the cell membrane (2); and cell depolarization opens voltage gated calcium channels (3) which leads to exocytosis of insulin containing vesicles(4).

Question 2

How does insulin regulate blood glucose levels?

Answer 2

1.Facilitating cellular glucose uptake, 2.Regulating carbohydrate, lipid and protein metabolism (How?) and 3.Promoting cell division and growth

Question 3

When is insulin therapy indicated?

Answer 3

In all Type 1 diabetes patients, and in
Type 2 diabetes patients with
1. Severe hyperglycaemia or
2. When glycemic targets are not reached with 2 or more oral hypoglycaemic agents (OHAs)

Question 4

What are the main types of insulins?

Answer 4

Rapid acting, short acting, intermediate acting and long acting

There is also ultra long acting

Question 5

Which of the insulin types has the longest peak duration of action?

Answer 5

NPH (Intermediate acting insulin)

Question 6

Which of the insulins are commonly used in an emergency to rapidly lower blood glucose levels?

Answer 6

Short acting regular human insulin
Note: It is administered intravenously

Question 7

Which of the insulins have the highest risk for hypoglycaemia?

Answer 7

NPH (Intermediate acting insulin) (Due to its longer peak action, greater intra/inter patient variability making it more unpredictable)

Question 8

Which insulins cannot be mixed with any other insulin in a single syringe?

Answer 8

Long-acting (Glargine, detemir) cannot be mixed with short or rapid-acting insulins in the same syringe

Question 9

What adverse effects are associated with insulin use?

Answer 9

Hypoglycaemia and lipodystrophy

Question 10

How is insulin commonly administered?

Answer 10

Subcutaneous injection

Question 11

What factors affect the absorption of insulin?

Answer 11

Site of injection, Depth of injection, Volume and concentration of the dose injected, exercise, heat (e.g. sitting in a sauna), massage of insulin site

Question 12

How does corticosteroids or an acute infection affect insulin demands?

Answer 12

It is likely to increase insulin demands as it can cause an increase in blood glucose levels (likely due to insulin resistance)

Question 13

Which oral hypoglycaemic agent is commonly used as the first line of treatment in the absence of any contraindications?

Answer 13

Metformin

Question 14

What is metformin’s mechanism of action?

Answer 14

Metformin decreases hepatic glucose production, increases the density of insulin receptors at the tissues and reduces intestinal glucose absorption

Question 15

What are the major side effects of Metformin?

Answer 15

Gastrointestinal issues, increased risk of Vitamin B12 deficiency, caution in renal problems.

Question 16

What factors could contraindicate the use of metformin?

Answer 16

Renal dysfunction, lactic acidosis, severe hepatic dysfunction

Question 17

What is thiazolidinedione’s mechanism of action?

Answer 17

Primary mechanism of action is via the activation of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ). PPAR-γ ligands are known to regulate glucose metabolism, adipogenesis, and improve insulin sensitivity at adipose tissues, liver and skeletal muscles.

Question 18

What are the key adverse effects associated with the use of thiazoldinediones?

Answer 18

Weight gain, peripheral edema, increased risk of heart failure (fluid retention) and bone fractures

Question 19

Will an obese patient be suitable for thiazolidinediones?

Answer 19

Ideally not recommended as the drug can cause weight gain

Question 20

What is sulfonylurea’s mechanism of action?

Answer 20

Sulfonyureas (SU) bind to the SU receptor proteins subunits of the KATP channels. Drug binding inhibits KATP channel mediated K+ efflux, triggering a calcium-dependent exocytosis of insulin granules from the pancreatic β-cells.

Question 21

Name a sulfonylurea with a long duration of action

Answer 21

Glibenclamide - High risk of hypoglycaemia compared to the others

Question 22

What are the key adverse effects associated with the use of sulfonylureas?

Answer 22

Weight gain, hypoglycaemia

Question 23

What patient profile may have a higher risk of hypoglycaemia with sulfonyureas?

Answer 23

Elderly, poor renal function, or hepatic dysfunction, people with irregular eating habits

Question 24

What is meglitinide’s mechanism of action?

Answer 24

Meglitinides bind and close the ATP-dependent potassium (KATP) channels on the pancreatic beta cells in a glucose-dependent manner stimulating insulin release

Question 25

Why are meglitinides commonly used at meal times?

Answer 25

They have a rapid onset and short duration of action, which helps control postprandial glucose levels by stimulating insulin release in response to meals.

Question 26

What is acarbose’s mechanism of action?

Answer 26

The α-glucosidase inhibitors reversibly inhibit membrane-bound α-glucosidase in the intestinal brush borders slowing down the rise in glucose levels after a meal

Question 27

What are some side effects associated with the use of acrbose?

Answer 27

Flatulence, GI discomfort

Question 28

In which groups of patients will acarbose be contraindicated?

Answer 28

Gastrointestinal diseases like Inflammatory bowel disease, severe renal and hepatic disease

Question 29

What are the 2 classes of drugs that work by incretin based therapy?

Answer 29

Dipeptidyl peptidasae-4 inhibitors, GLP-1 receptor agonist

Question 30

What are the mechanisms of action of DPP-4 inhibtors?

Answer 30

DPP-4 inhibitors binds and inhibits DPP-4 thus prolonging the action of the endogenous incretins, which then stimulate pancreatic β-cells to increase glucose-stimulated insulin release, and suppress α-cell mediated glucagon release and hepatic glucose production.

Question 31

Name 2 DPP-4 Inhibitors

Answer 31

Sitagliptin, Linagliptin

Question 32

Name 2 examples of glucagon-like 1 peptide 1-receptor agonist

Answer 32

Liraglutide, Semaglutide

Question 33

How are GLP-1 receptor agonists administered?

Answer 33

Subcutaneous injection
Semaglutide is also available as an oral tablet

Question 34

What are the mechanisms of action of glucagon-like 1 peptide 1-receptor agonist?

Answer 34

They activate the GLP-1 receptor, a membrane-bound cell-surface receptor in pancreatic beta cells to increase insulin release in the presence of elevated glucose concentrations.
They delay gastric emptying, leading to slower glucose absorption from the gastrointestinal tract.
This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia.

Question 35

What are the potential adverse effects associated with the use of DPP-4 inhibitors and GLP-receptor agonist?

Answer 35

GI related issues, pancreatitis (not recommended for patients with a history of pancreatitis

Question 36

Other benefits of GLP-1 receptor agonists

Answer 36

Weight loss, improved cardiovascular outcomes

Question 37

What are examples of sodium glucose co-transporters?

Answer 37

Dapagliflozin, empagliflozin

Question 38

What is SGLT-2’s mechanism of action?

Answer 38

SGLT2, expressed in the proximal renal tubules, is responsible for 90% of the reabsorption of filtered glucose from the tubular lumen. By inhibiting SGLT2, reabsorption of filtered glucose is reduced and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.

Question 39

What other benefits does SGLT-2 have?

Answer 39

Favourable cardiac outcomes - including reduced risk of hospitalizaton due to heart failure and reduced risk of worsening renal function

Question 40

What are some of the key adverse effects associated with the use of SGLT-2 inhibtors?

Answer 40

Urinary tract infection, and increased urination, female genital mycotic infections, increased risk of lower limb amputation (Canagliflozin), diabetic ketoacidosis

Question 41

Which hypoglycaemic agents are associated with weight gain?

Answer 41

sulfonyureas, thiazolidinediones, meglitinides

Question 42

Which hypoglycaemic agents have been found to have significant cardiovascular benefits and are favoured for patients with Atherosclerotic cardiovascular disease?

Answer 42

SGLT-2 inhibitors, GLP-1 receptor agonist

Question 43

What distinguishes Meglitinides like Repaglinide from Sulfonylureas?

Answer 43

Meglitinides stimulate insulin release in a glucose-dependent manner and have a rapid onset and short duration of action.