Diabetes Medications and their Classes

• Diabetic Medications, Dosages, and Routes (non-insulin).
• Five Mechanisms used to lower blood sugars.
• Insulin types, onset, and duration of action.
• Injectable Diabetes Medications.
• Diabetes Medications that promote Weight Loss.
• Diabetes Medications that promote weight gain.

There are 10 classes of common diabetes medications to know. Only 3 of them are injectables. The other 7 are oral. The three injectable classes are GLP-1 receptor agonists (e.g. liraglutide), Amylin analog (e.g. Pramlintide), and insulins (e.g. insulin glargine)

 Decrease Gluconeogenesis

1. Biguanides (e.g. Metformin). Metformin is 1st-line. It decreases hepatic gluconeogenesis. It is also an insulin sensitizer.
S/E: GI effects (N/V/D) in <10% of pts; discontinuation rate is <1%. Should not be used in pts with eGFR <30. Use with caution in eGFR between 30 and 45. Assoc w/ B12 deficiency.
Metformin 500 to 1000 mg PO BID
Combination with Other Drugs:
Janumet (Sitagliptin/Metformin) 50/500-1000mg PO BID
Invokamet (Canagliflozin/Metformin) 50/500-1000 mg PO BID. You also have 150/500 and 150/1000
Glipizide/metformin 2.5/250; 2.5/500; 5/500

Insulin Secretagogues, etc.

Both insulin secretagogues and incretin-based medications have MOAs that lead to increased insulin secretion by the beta cells of the pancreas. The secretagogues cause direct Beta cell insulin secretion while the GLP1-receptor agonists and DPP-4 inhibitors do it indirectly through incretins by mimicking them (GLP-1R agonists) or preventing their degradation (DPP-4i). *** Incretins only stimulate glucose-dependent insulin secretion — i.e. insulin secretion with meals that have glucose.

2. Sulfonylureas e.g. Glipizide, Glyburide, Glimepiride – Directly stimulate beta-cells in the pancreas to release insulin. Glipizide (shorter 1/2 life of ~2-5h). Glyburide (glibenclamide) and glimepiride both have longer 1/2 lives of 10h and 9.2h respectively. All of them are metabolized by the liver and excreted heavily by the kidneys. Small amounts also excreted in feces. Elderly patients and patients with CKD at risk of hypoglycemia 2/2 to long half-lives and the fact that they are excreted by the kidneys.
-They have a high failure rate over time 2/2 to beta-cell burnout leading to decrease beta-cell function.
S/E: Weight gain and hypoglycemia. Use with caution in pts with liver and renal disease. Contraindicated in patients with sulfa allergy. May cause hemolytic anemia in pts w/ G6PD deficiency.

3. Glinides(Meglitinides) e.g. repaglinide (Prandin) and nateglinide – Also cal. Directly stimulate beta-cells in the pancreas to release insulin. Glinides are non-sulfonylureas that act on a portion of the sulfonylurea receptor to stimulate insulin secretion. As such, the MOA is similar to that of sulfonylurea. Their names end in glinide e.g. repaglinide (Prandin) and nateglinide.
-Assoc with weight gain and hypoglycemia (especially with concurrent use of insulin or sulfonylurea). A slight increase in serum uric acid levels is seen.

Incretin-Based Medications

4. GLP–1 Receptor Agonists e.g. Liraglutide (Victoza) and Exenatide (Byetta). Note that their names end in -tide (peptide) and they are injectables.
Glucagon-like peptide-1 (GLP-1) and GIP are examples of incretins, a group of hormones that stimulate the pancreas to make insulin. Incretin receptor agonists (also called incretin mimetics) mimick incretins and act on incretin receptors stimulating the pancreas to make insulin. The incretin mimetics currently being used are GLP-1 receptor agonists.  They work by activating the GLP-1 receptors, which increases insulin secretion, decreases glucagon secretion, slows or delays gastric emptying, and increases satiety. Because these drugs increase satiety, they are associated with weight loss. GLP-1 analogs.
–Associated w/ weight loss.
S/E: Associated with pancreatitis. Need to adjust the dose in CKD.
GLP-1 agonists are contraindicated in patients with medullary thyroid cancer or multiple endocrine neoplasm syndrome, or with a family history of these conditions.
*Agonist=analog. GLP-1 receptor agonist=Glucagon-like Peptide-1 receptors agonists.

5. DPP-4  inhibitors (Gliptins) e.g. Sitagliptin (Januvia). Oral Rx.
Dipeptidyl Peptidase-4 (DPP-4 ) inhibitors block degradation of incretins (GLP-1 & GIP). Incretins stimulate the pancreas to make insulin. Dipeptidyl Peptidase-4 breaks down incretins as a control mechanism. By blocking the degradation of incretins, DPP-4 inhibitors increase incretin levels (GLP-1, GIP), and as such increase insulin secretion. KTA: They work through a mechanism similar to the SSRIs. GLP-4 inhibitor’s names end in gliptin. E.g. Sitagliptin (Januvia)
-They are weight neutral.
S/E: Associated with pancreatitis. Need to adjust the dose in CKD.

 Decrease carbohydrate breakdown and absorption from the GI tract.

6. Alpha-glucosidase inhibitors e.g.  Acarbose. Oral Rx. They inhibit carbohydrate breakdown (metabolism) in the GI tract by competitively inhibiting alpha-glucosidases (enzymes that break down complex carbohydrates into monosaccharides).
S/E: Severe GI intolerance (e.g. bloating, diarrhea, flatulence in > 50% of pts).
Don’t use in pts w/ cirrhosis or CKD (serum creatinine > 2)

7. Amylin analog e.g. Pramlintide. Injectable Rx.  Acarbose and amylin analogs work in a similar way. Acarbose inhibits GI tract carbohydrate metabolism and amylin analogs decrease carbohydrate absorption and GI motility.
–Associated with weight loss. When used with insulin can cause severe hypoglycemia.
–Don’t use in patients with gastroparesis or osteopenia b/c it decreases GI mobility and decreases absorption.

 Insulin Sensitizers

8. Thiazolidinediones e.g. pioglitazone (Actos). Works by increasing insulin sensitivity (i.e. it reduces insulin resistance).
S/E: Assoc with weight gain, CHF exacerbation, increase in fractures, hepatotoxicity, edema. Rarely, bladder cancer. Need to monitor LFTs.

Take sugars out of the body

9. SGLT-2 inhibitor (Gliflozins). E.g. Empagliflozin, Dapagliflozin, and Canagliflozin (Invokana). They promote glucosuria. Gliflozins inhibit the sodium-glucose transporter-2 (SGLT-2) in the kidney.
Associated with:
-Weight loss.
-UTIs.
“SGLT2 inhibitors are not as safe or effective if the patient’s estimated glomerular filtration rate (eGFR) is <50 mL/min/1.73 m2, and it is not recommended in patients with an eGFR <30 mL/min/1.73 m2.”

10. Insulins

S/E: Weight gain, hypoglycemia. Injection, lipodystrophy. 
Different types of insulin.