Drugs used in the management of Diabetes Mellitus

Question 1

Which glucose transporter is found at the pancreatic beta cells?

Answer 1

GLUT 2

Question 2

How does an increase in glucose level stimulate insulin release?

Answer 2

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 closing of the potassium channels and depolarization of the cell (2); and cell depolarization opens voltage gated calcium channels (3) which leads to exocytosis of insulin containing vesicles(4).

Question 3

How does insulin regulate blood glucose levels?

Answer 3

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

Question 4

How is exogenous insulin mainly cleared?

Answer 4

Kidneys

Question 5

When is insulin therapy indicated?

Answer 5

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 6

What are the main types of insulins?

Answer 6

Rapid acting, short acting, intermediate acting and long acting
Degludec can be called ultra long acting

Question 7

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

Answer 7

NPH (Intermediate acting insulin)

Question 8

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

Answer 8

Short acting regular human insulin
Note: It is administered intravenously

Question 9

Which of the insulins have the highest risk for hypoglycaemia?

Answer 9

NPH (Intermediate acting insulin)

Question 10

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

Answer 10

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

Question 11

What adverse effects are associated with insulin use?

Answer 11

Hypoglycaemia and lipodystrophy

Question 12

How is insulin commonly administered?

Answer 12

Subcutaneous injection

Question 13

What factors affect the absorption of insulin?

Answer 13

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 14

How does corticosteroids or an acute infection affect insulin demands?

Answer 14

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

Question 15

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

Answer 15

Metformin

Question 16

What is metformin’s mechanism of action?

Answer 16

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

Question 17

What factors could contraindicate the use of metformin?

Answer 17

Renal dysfunction, lactic acidosis, hepatic dysfunction

Question 18

What is thiazolidinedione’s mechanism of action?

Answer 18

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 19

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

Answer 19

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

Question 20

Will an obese patient be suitable for thiazolidinediones?

Answer 20

Ideally not recommended as the drug can cause weight gain

Question 21

What is sulfonylurea’s mechanism of action?

Answer 21

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 22

Name a sulfonylurea with a long duration of action

Answer 22

Glibenclamide - High risk of hypoglycaemia compared to the others

Question 23

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

Answer 23

Weight gain, hypoglycaemia

Question 24

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

Answer 24

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

Question 25

What is meglitinide’s mechanism of action?

Answer 25

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

Question 26

Why are meglitinides commonly used at meal times?

Answer 26

They have a rapid onset and short duration of action

Question 27

What is acarbose’s mechanism of action?

Answer 27

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 28

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

Answer 28

Flatulence, GI discomfort

Question 29

In which groups of patients will acarbose be contraindicated?

Answer 29

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

Question 30

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

Answer 30

Dipeptidyl peptidasae-4 inhibitors, GLP-1 receptor agonist

Question 31

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

Answer 31

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 32

Name 3 DPP-4 Inhibitors

Answer 32

Sitagliptin, Linagliptin and Vildagliptin

Question 33

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

Answer 33

Liraglutide, Semaglutide

Question 34

How are GLP-1 receptor agonists administered?

Answer 34

Subcutaneous injection
Semaglutide is also available as an oral tablet

Question 35

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

Answer 35

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. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia.

Question 36

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

Answer 36

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

Question 37

Other benefits of GLP-1 receptor agonists

Answer 37

Weight loss, improved cardiovascular outcomes

Question 38

What are examples of sodium glucose co-transporters?

Answer 38

Dapagliflozin, empagliflozin, canaglifloziin

Question 39

What is SGLT-2’s mechanism of action?

Answer 39

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 40

What other benefits does SGLT-2 have?

Answer 40

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

Question 41

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

Answer 41

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

Question 42

Which hypoglycaemic agents are associated with weight gain?

Answer 42

sulfonyureas, thiazolidinediones, meglitinides

Question 43

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

Answer 43

SGLT-2 inhibitors, GLP-1 receptor agonist