Administering non-insulin therapies for diabetes mellitus

The American Diabetes Association (ADA) 2026 Standards of Care

provide guidance on initiating pharmacologic treatment for type 2

diabetes (DM2)

emphasize a person-centered approach that considers comorbidities, patient preferences, cost and access, hypoglycemia risk, and potential medication side effects

Medication if the Adult with DM2 has Cardiovascular Disease Or High Cardiovascular Risk:

• SGLT2 inhibitors (empagliflozin or canagliflozin)

• GLP-1 receptor agonist (semaglutide)

medication if the adult with DM2 has HF

SGLT2

Benefits to taking SGLT2 for an Adult with DM2 has HF

increased urinary sodium and water excretion, reduced blood pressure and cardiac workload, improved cardiac energy metabolism, and reduced inflammation.

Medication if adult with DM2 has obesity

• GLP-1 receptor agonist (semaglutide, dulaglutide, liraglutide)

• Dual GIP and GLP-1 receptor agonist (tirzepatide)

Medication if the adult with DM2 has chronic kidney disease

• SGLT-2

• GLP-1 receptor agonist - semaglutide

Medication if the adult with DM2 has MASH

• GLP-1 agonist or dual GIP and GLP-1 receptor or

• pioglitazone

• SGLT2 inhibitors

• combination of GLP-1 receptor agonist, SGLT2 inhibitors and pioglitazone

When to initiate insulin

should be considered right away ( before or alongside other drugs) if:

• A person is showing hyperglycemia symptoms,

or

• A person has very high blood sugar levels, such as A1C >10% or blood glucose ≥300 mg/dL

A1C that require insulin

>10%

Metformin indication

common initial option for people who mainly need glucose lowering and have no other conditions that favor a different medication.

Metformin advantages

• inexpensive

• does not cause weight gain

• low risk of hypoglycemia

• offers cardiovascular benefits

Metformin side effect

• GI effects - diarrhea and abdominal discomfort

• long-term can contribute to vitamin B12 deficiency

Metformin contraindication

eGFR below 30mL/min/1.73

Selective sodium-glucose transporter-2 inhibitors (SGLT2i) prototypes

• Dapagliflozin (Farxiga)

• Empagliflozin ( Jardiance)

• Canagliflozin (Invokana)

Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA) prototypes

• Semaglutide ( Ozempic® , Rybelsus)

• Dulaglutide (Trulicity ® )

• Liraglutide (Victoza ®)

Dual Glucose-dependent Insulinotropic Polypeptide (GIP) agonist and Glucagon-like Peptide-1 (GLP-1) receptor agonist (Dual GIP and GLP-1 RA) prototype

tirzepatide (mounjaro)

Biguanides prototypes

• metformin

• glucophage

Dipeptidyl Peptidase-4 Inhibitors (DDP-4i) prototype

sitagliptin (januvia)

Thiazolidinediones (TZDs or Glitazones) prototype

pioglitazone (actos)

Sulfonylureas prototype

• Glipizide (Glucotrol or Glucotrol XL)

• Glyburide (DiaBeta)

• Glimepiride (Amaryl)

Insulin prototype

• insulin glargine (lantus)

• insulin detemir (levemir)

• insulin degludec (tresiba)

insulin indication

• glucose goals are not achieved with other therapies or when hyperglycemia is severe and symptomatic

• A1C above goal and is on GLP1 or dual GIP/GLP1 and basal insulin

• pregnant

sulfonylureas indication

• use associated with hypoglycemic episodes - lose effectiveness over tie

• not recommended with CKD

Thiazolidinediones indication

for pts with coexisting MASH

DDP-4i indication

• add on for inadequatly controlled on metformin

• not combined with GLP-agonist

• monotherapy if can’t tolerate with metformin

• do not progress diabetic kidney disease

Biguanides indication

• when glucose lowering is the primary treatment needed

• for high-risk adults for prediabetes

• reduce risk of major adverse cardiovascular events

GIP/GLP1 indication

• when main goal to reduce A1C and weight loss

• found to decrease progression of diabetic kidney disease, HF, and MASH

• approved for T2DM in adults and children 10+

GLP1 indication

• first line therapy for DM2 and those who are overweight

• treatment for MASH

• intervention for ppl with concurrent CVD, HF, and/or CKD

SGLT21 indication

• first line therapy for ppl with CVD, HF, and CKD

• decrease progression diabetic kidney disease

• T2DM in adults and children 10+

treatment for HFrEF and HFpEF

dapagliflozin and empagliflozin

SGLT2 contraindication

• hx of DKA

• high risk of bone fractures

• pregnancy

GLP1 contraindication

• family hx of medullary thyroid cancer

• multiple endocrine neoplasia syndrome 2

• high risk for pancreatitis and/or gallbladder disease

• people with gastroparesis

• pregnancy

• <18 years

GIP/GLP1

• family hx of medullary thyroid cancer

• multiple endocrine neoplasia syndrome 2

• high risk for pancreatitis and/or gallbladder disease

• people with gastroparesis

• pregnancy

• <18 years

biguanides contraindication

ppl with kidney disease (eGFR <30)

DDP-4i contrainidcation

• pregnancy

• children with T2DM

thiazolidinediones contraindication

• HF

• risk of bone fracture

• active or hx of bladder Ca

• pregnancy

sulfonylureas contraindication

pregnancy

Insulin MOA

• Maintains normal blood glucose levels by facilitating cellular glucose uptake.

• It also stimulates the liver to store glucose as glycogen

sulfonylureas MOA

Lowers blood glucose by stimulating the release of insulin from the pancreas

thiazolidinediones MOA

• Increases insulin sensitivity by acting on adipose tissue and muscle to increase glucose utilization.

• May also reduce glucose production in the liver.

• Improves fibrosis and decreases inflammation and steatosis with NASH.

DDP-4i MOA

• These drugs enhance the action of the incretin hormones

GLP-1 and GIP.

• They block the action of Dipeptidyl peptidase-4 (DPP- 4), an enzyme that inactivates incretin hormones. Therefore, they lower blood glucose by prolonging the effect of incretins

Biguanides MOA

• Mostly suppresses gluconeogenesis. Inhibits glucose production in the liver.

• Increases glucose uptake in skeletal muscle, fat, and liver cells to decrease insulin resistance.

• Slightly reduces intestinal glucose absorption.

• Can lower serum lipids, including LDL and triglycerides

GIP/GLP1 MOA

lower both fasting and postprandial blood glucose levels and support weight management in people with type 2 diabetes or obesity

GLP-1 MOA

Activates receptors on the incretin hormone glucagon-like peptide-1 to lower blood glucose

SGLT2 MOA

Activates receptors on the incretin hormone glucagon-like peptide-1 to lower blood glucose

SGLT 2 side effects

• genital fungal infection

• UTI

• hypotension an dehydration → AKI (rare)

• bone fractures

GLP1 side effects

• GI intolerance - diminish over tim e

• fatigue

• AKI

• injection site irritation

• diabetic retinopathy

GIP/GLP1 side effects

• GI intolerance - diminish over tim e

• fatigue

• AKI

• injection site irritation

• diabetic retinopathy

Biguanides

• GI intolerance

• long-term use b12 deficiency

• lactic acidosis

DDP-4i

• well tolerated

• inflammed skin

• joint pain

• pancreatitis (rare)

thiazolidinediones side effects

• fluid retention and HF (rare)

• deceased bone density

• increased risk of bladder cancer

• liver failure (rare)

sulfonylureas side effects

hypoglycemia more likely ppl with CKD or liver failure

insulin side effects

• risk of hypoglycemia

• injection site irritation

insulin nursing administration considerations

• monitor s/s hypoglycemia

• start with low dose and titrade

• analog insulin cause less hypoglycemia and weight gain and lower A1C

sulfonylureas nursing administration considerations

• monitor s/s of hypoglycemia

• when combined with alcohol can cause disulfiram like reaction

disulfiram like reaction

• N/V,

• abdominal cramps,

• flushing,

• dizziness,

• headache, and

• hypoglycemia

thiazolidinediones nursing administration considerations

teach pts to monitor for edema, weight gain, and s/s of HF

DDP-4i nursing administration considerations

• Monitor for hypersensitivity reaction (anaphylaxis or angioedema).

• Observe patients for signs and symptoms of pancreatitis.

Biguanides nursing administration considerations

• dose initially titrated

• with meals

• a1c, fasting glucose, and kidney function monitored

• metformin withheld before administration with contrast media

GLP1 nursing administration considerations

• dose initially titrated up

• small meals, reduce spicy and high fat

• monitor abdomen pain

• rotate injection

• close monitoring of retinopathy

• liquid only diet for 24 h before procedure

GIP/GLP1 nursing administration considerations

• dose initially titrated up

• small meals, reduce spicy and high fat

• monitor abdomen pain

• rotate injection

• close monitoring of retinopathy

• liquid only diet for 24 h before procedure

SGLT2 nursing consideration

• monitor for infection and UTI

• discontinue if suspected DKA

• monitor volume status, BP, and renal function

• discontiue 3-4 days before surgery, during critical illness