Endocrine System - Drugs for Diabetes Mellitus

What is the insulin difference between type 1 and type 2 diabetes mellitus?

Type 1 diabetes mellitus results in an absolute insulin deficiency, meaning no insulin is produced

Type 2 diabetes mellitus results in a relative insulin deficiency, meaning some insulin is still produced

What is the cause of type 1 diabetes?

The body develops antibodies that attack the pancrease, resulting in no insulin being produced and a sudden onset of the condition

What is the cause of type 2 diabetes?

Insulin receptors become desensitized to glucose, resulting in the pancreas increasing insulin production. The beta cells of the pancreas becoming exhausting, resulting in cell death and decreased insulin production.

The decreased insulin production results in increased blood glucose levels

What are best practice pharmacotherapies for T1DM?

1. Multiple daily injections of insulin (MDI), requiring bolus and basal insulin

2. Use of continuous subcutaneous insulin infusions (CSII) via an insulin pump that only uses bolus insulin - can be adjusted by the individual during mealtime or exercise

What is basal insulin?

Background insulin that addresses hepatic glucose production - long acting throughout the day

Used in daily insulin injections

What is bolus insulin?

Insulin that is secreted in response to energy intake and glucose during mealtime - rapid short lasting action

Used in daily insulin injections and CSII insulin pumps

What is a common adverse effect of insulin injection for TIDM treatment?

Hypoglycemia

Should provide patient education

What are the 7 drug classes that are used for treatment of T2DM?

1. Metformin - 1st line

Commonly used drug classes

2. Incretin enhancers (GLP-1 + DPP-4)

3. SGLT2 inhibitors

Less commonly used drug classes

4. Alpha glucosidase inhibitors

5. Meglitinides

6. Sulphonylureas

7. Thiazolidinediones

What are biguanides? (Use, Mechanism, Adverse effects)

Use

Used as first line therapy for treatment of T2DM

Mechanism

Decreases hepatic production of glucose and reduces insulin resistance (increase insulin sensitivity and glucose uptake by tissues)

Adverse effects

0 effect on hypoglycemia

0 effect on weight

~ Some GI side effects (abdo pain, nausea, vomiting, diarrhea)

Includes metformin

What is the use of biguanides?

Used as first line therapy for treatment of T2DM

What is the mechanism of action of biguanides?

Decreases hepatic production of glucose and reduces insulin resistance (increase insulin sensitivity and glucose uptake by tissues)

What are adverse effects of biguanides?

Adverse effects

0 effect on hypoglycemia

0 effect on weight

~ Some GI side effects (abdo pain, nausea, vomiting, diarrhea)

Can be avoided by starting on a small dose, and gradually increasing until dose is fit for patient

What is the role of second line therapies of T2DM?

Used when management of diabetes is insufficient with first-line treatment - metformin

Can be used to treat other pathophysiological processes associated with type 2 diabetes, especially cardiovascular and renal health.

Thus the treatment should be patient-centered to address their needs

What is the general role of incretins?

Hormones secreted by the intestines in response to food

Signals the pancreases to increase insulin secretion and for the liver to stop producing glucagon, lowering blood glucose levels

What are GLP1 receptor agonists? (Use, mechanism, adverse effects)

Use

Used as second line pharmacological treatment for patients with T2DM. Has protective effect on cardiovascular and renal systems. Commonly used

Mechanism

Mimics incretin, stimulating the pancreas to increase insulin secretion, stops the liver from producing glucagon, slows gastric emptying, and increases satiety, resulting in lowered blood glucose levels

Adverse effects

0 effect on hypoglycemia

SIGNIFICANT effect on weight loss

GI related effects (nausea, vomiting, diarrhea, constipation)

What is the use of GLP1 receptor agonists?

Used as second line pharmacological treatment for patients with T2DM. Has protective effect on cardiovascular and renal systems. Commonly used

What is the mechanism of action of GLP1 receptor agonists?

Mimics incretin, stimulating the pancreas to increase insulin secretion, stops the liver from producing glucagon, slows gastric emptying, and increases satiety, resulting in lowered blood glucose levels

What are the adverse effects of GLP1 receptor agonists?

0 effect on hypoglycemia

SIGNIFICANT effect on weight loss

GI related effects (nausea, vomiting, diarrhea, constipation)

What are DPP-4 inhibitors? (Use, Mechanism, Adverse effects, Drug-Drug interaction)

Use

Used as second line pharmacological treatment for patients with T2DM. Commonly used

Mechanism

Blocks DPP-4 enzyme, which breaks down incretin hormones. Results in increased incretin hormones

Adverse effects

0 effect on hypoglycemia

0 effect on weight

Drug-drug interactions

Should not be used in combination with other incretins

What is the use of DPP-4 inhibitors?

Used as second line pharmacological treatment for patients with T2DM. Commonly used

What is the mechanism of action of DPP-4 inhibitors?

Blocks DPP-4 enzyme, which breaks down incretin hormones. Results in increased incretin hormones

What are the adverse effects of DPP-4 inhibitors?

0 effect on hypoglycemia

0 effect on weight

What are SGLT-2 inhibitors? (Use, Mechanism, Adverse Effect)

Use

Used as second line pharmacological treatment for patients with T2DM. Has protective effect on cardiovascular and renal systems. Commonly used

Mechanism

Inhibits SGLT2 proteins, resulting in reduced glucose reabsorption by the kidneys -> increased urinary glucose excretion

Adverse Effects

0 effect on hypoglycemia

Weight loss

What is the use of SGLT-2 inhibitors?

Used as second line pharmacological treatment for patients with T2DM. Has protective effect on cardiovascular and renal systems. Commonly used

What is the mechanism of action of SGLT-2 inhibitors?

Inhibits SGLT2 proteins, resulting in reduced glucose reabsorption by the kidneys -> increased urinary glucose excretion

What are adverse effects of SGLT-2 inhibitors?

0 effect on hypoglycemia

Weight loss

What are alpha-glucosidase inhibitors? (Use, Mechanism, Adverse effect)

Use

Used as second line pharmacological treatment for patients with T2DM. Not as commonly used

Mechanism

Inhibits pancreatic amylase and intestinal glucosidase, delaying breakdown and absorption of complex carbohydrates

Adverse Effects

Minor GI effects (flatulence, diarrhea, abdominal distension)

0 effect on hypoglycemia

0 effect on weight

What is the use of alpha-glucosidase inhibitors?

Used as second line pharmacological treatment for patients with T2DM. Not as commonly used

What is the mechanism of action of alpha-glucosidase inhibitors?

Inhibits pancreatic amylase and intestinal glucosidase, delaying breakdown and absorption of complex carbohydrates

What are adverse effects of alpha-glucosidase inhibitors?

Minor GI effects (flatulence, diarrhea, abdominal distension)

0 effect on hypoglycemia

0 effect on weight

What are sulfonylureas and meglitinides? (Use, mechanism, adverse effects)

Use

Used as second line pharmacological treatment for patients with T2DM. Not as commonly used

Mechanism

Activates sulfonylurea receptor on pancreatic beta-cells to stimulate insulin secretion

Adverse effects

Minimal/Moderate risk for hypoglycemia

Weight gain

What is the use of sulfonylureas and meglitinides?

Used as second line pharmacological treatment for patients with T2DM. Not as commonly used

What is the mechanism of action of sulfonylureas and meglitinides?

Activates sulfonylurea receptor on pancreatic beta-cells to stimulate insulin secretion

What are adverse effects of sulfonylureas and meglitinides?

Minimal/Moderate risk for hypoglycemia

Weight gain

What are thiazolidinediones? (Use, mechanism of action, adverse effects)

Use

Used as second line pharmacological treatment for patients with T2DM. Not as commonly used

Mechanism

Decreases release of glucose from the liver

Increases insulin sensitivity in adipose and muscle tissue

Adverse effects

Cardiovascular effects (edema, heart failure, myocardial infarction)

Higher occurrence of fractures

Weight gain

0 effect on hypoglycemia

What is the use of thiazolidinediones?

Used as second line pharmacological treatment for patients with T2DM. Not as commonly used

What is the mechanism of action of thiazolidinediones?

Decreases release of glucose from the liver

Increases insulin sensitivity in adipose and muscle tissue

What are the adverse effects of thiazolidinediones?

Cardiovascular effects (edema, heart failure, myocardial infarction)

Higher occurrence of fractures

Weight gain

0 effect on hypoglycemia

Which two drug classes used for the treatment of type 2 diabetes mellitus also has protective effects on cardiovascular and renal health?

SGLT2 inhibitors and GLP1-RAs

Can decrease risk of cardiovascular diseases, heart failure, and chronic kidney diseases associated with diabetes

Which of the 7 drug classes used for treatment of type 2 diabetes mellitus has adverse effects for hypoglycemia?

Sulfonylureas and Meglitinides - minimal moderate risk for hypoglycemia

Which of the 7 drug classes for treatment of type 2 diabetes mellitus has adverse effects for weight changes?

1. GLP1 receptor agonists (weight loss)

2. SGLT2 inhibitors (weight loss)

3. Sulfonylureas and Meglitinides (weight gain)

4. Thiazolidinediones (weight gain)