Non-insulin management of

diabetes mellitus
Outline
Oral hypoglycemic pharmacology
A1C goals in DM
Main types of therapies
Non-insulin hypoglycemics by class
Drug class Mechanism of action Generic vs (brand) Advantages Disadvantages Expected
name A1C
decrease
Biguanide - Decreases hepatic Metformin -CV events GI disturbances 1.0 to 1.3%
gluconeogenesis -rare hypoglycemia B12 deficiency (anemia,
peripheral neuropathy)

Lactic acidosis
- CI if GFR < 30 ml/min, acidosis,
hypoxia, dehydration

Sulfonylurea - Closes K+ channel in Glimepiride (Amaryl) - Microvascular risk Hypoglycemia 0.4% to 1.2%
beta-cells Glipizide (Glucotrol) - Postprandial Wt gain
increases insulin Glyburide glucose
secretion

Meglitinide - Closes K+ channel in Nateglinide (Starlix) - Postprandial Hypoglycemia 0.5% to 1.0%

beta-cells Repaglinide (Prandin) glucose Wt gain
increases insulin
secretion
Drug class Mechanism of action Generic vs (brand) Advantages Disadvantages Expected A1C
name decrease
Glucagon-like peptide- - Increases insulin Albiglutide (Tanzeum) - Rare hypoglycemia - GI disturbances 0.8% to 2.0%
1 (GLP-1) analog secretion Dulaglutide (Trulicity) -Wt loss - Wt loss
- Decreases Exenatide (Byetta) - Acute pancreatitis
glucagon Liraglutide (Victoza) (rare)
secretion -C-cell hyperplasia
- Delays gastric -Medullary thyroid
emptying tumors

-injectable
Dipeptidylpeptidase-4 Increases GLP-1 levels Alogliptin (Nesina) -Rare hypoglycemia - Angioedema/urticaria 0.5% to 0.9%
(DPP-4) inhibitor Linagliptin (Tradjenta) - Acute pancreatitis
Saxagliptin (Onglyza) (rare)
Sitagliptin (Januvia)

Amylin analog - Delays gastric Pramlintide (Symlin) Wt loss GI disturbances 0.5%

emptying
(increases satiety) Injectable
- Decreases
glucagon
secretion
Drug class Mechanism of action Generic vs (brand) name Advantages Disadvantages Expected A1C
decrease
Sodium-glucose - Inhibits Canagliflozin (Invokana) - Blood GU infection 0.5% to 0.9%
cotransporter 2 resorption of Dapagliflozin (Farxiga) pressure Polyuria
(SGLT-2) inhibitor Na/glucose co- Empagliflozin (Jardiance) -Wt loss Increases LDL-C
transporter in Volume depletion
proximal
convoluted Renally-dosed
tubules

Alpha-glucosidase - Inhibits intestinal Acarbose (Precose) Rare GI disturbances 0.5% to 0.8%

inhibitor brush-border alpha- Miglitol (Glyset) hypoglycemia
glucosidases
Thiazolidonedione - Increases insulin Pioglitazone (Actos) Rare -Wt gain 0.5% to 1.4%
sensitivity Rosiglitazone (Avandia) hypoglycemia -Edema, heart failure
-Bone fracture
-Increases LDL-C
What are the A1C targets we are trying to
reach?
Hb A1C goals in DM type 2
A1C 7%: mostly healthy, nonpregnant adults

A1C 7.5 8%: patients with short life expectancy, CV disease, diabetes
duration of 10+ yrs

Initial management based on initial A1C and or symptoms at time of

presentation
What is the initial drug used as non-insulin
therapy? Why?
Types of therapies
Monotherapy
Metformin + (lifestyle)

Dual therapy
Metformin + 1 hypoglycemic + (lifestyle)

Triple therapy
Metformin + 2 hypoglycemics (includes basal insulin) + (lifestyle)

Combination injectable therapy

Metformin + basal insulin + bolus insulin(s) OR GLP-1 analog
How long do we trial a hypoglycemic drug
(without adverse effects)?
 Types of therapies
If initial A1C is 9% </= A1C < 10% may start dual therapy
If initial A1C is >/= 10% OR BG >/= 300 OR symptomatic may start Combination injectable therapy

Monotherapy
If target A1C is not achieved after 3mo

Dual therapy
If target A1C is not achieved after 3mo

Triple therapy
If target A1C is not achieved after 3mo

Combination injectable therapy

Combination
injectable therapy
How affordable are these medications?
Monthly cost of medications
References
American Diabetes Association. Standards of Medical Care in
Diabetes2017. The Journal of Clinical and Applied Research and
Education. January 2017.

George, Christa, Will, KAYLEY, Howard-Thompson Amanda.

Management of Blood Glucose with Noninsulin Therapies in Type 2
Diabetes. American Family Physician. July 2015.