ES Type II Diabetes

Sulfonylurea examples

- glipizide

- glyburide

- glimepiride

Meglitinide examples

- nateglinide

- repaglinide

Biguanides examples

metformin

Alpha-glucosidase inhibitor examples

- acarbose

- miglitol

DPP-4 inhibitor examples

- sitagliptan

- saxagliptan

- linagliptan

- alogliptan

Thiazolidinediones (TZDs) examples

pioglitazone

SGLT-2 inhibitor examples

- canagliflozin

- dapagliflozin

- empagliflozin

- ertugliflozin

- bexagliflozin

Oral GLP-1 Receptor Agonist examples

semaglutide

GLP-1 Receptor agonist examples

- liraglutide

- dulaglutide

- semaglutide

Dual GIP/GLP1 agonist

tirzepatide

Incretin effect

incretin hormones stimulate insulin secretion in response to nutrients entering GI tract

GLP-1 effects

- increases glucose-dependent insulin secretion

- suppresses glucagon

- slows gastric emptying

- increases satiety

SGLT2 role in kidneys

reabsorb glucose from urine back into the blood

Screening recommendations for T2DM

- ADA recommends screening for T2DM every 3 years in all adults beginning at age 35

- testing should be considered for individuals younger than 35 years w/ overweight or obesity who have additional risk factors

Risk factors for T2DM

- habitually inactive

- first-degree relative w/ diabetes

- member of high-risk ethnic populations

- hypertensive (or on therapy for HTN)

- HDL cholesterol <35 mg/dL and/or TG level >350 mg/dL

- PCOS

- other clinical conditions associated with insulin resistance

- history of CV disease

What is oral first drug of choice in a T2DM patient w/o any extra conditions or complications?

metformin

Medication choice for ASCVD

GLP-1 RA w/ proven CVD benefit

Medication choice for indicators of high CV risk

SGLT2i w/ proven CVD benefit

Medication choice for HF

- current or prior symptoms of HFrEF or HFpEF = SGLT2i w/ proven HF benefit

- symptomatic HFpEF and obesity = SGLT2i and/or GIP/GLP1 RA or GLP 1 RA w/ proven benefit for HF

Medication choice for chronic kidney disease (once on maximally tolerated dose of ACEi or ARB)

- SGLT2i w/ primary evidence of reducing CKD progression

- GLP-1 RA w/ proven CKD benefit

Medication choice for weight management: very high efficacy

semaglutide, tirzepatide

Medication choice for weight management: high efficacy

dulaglutide, liraglutide

Medication choice for weight management: intermediate efficacy

GLP-1 RA, SGLT2i

Medication choice for weight management: neutral efficacy

metformin, DPP-4i

When to add insulin to T2DM regimen

- symptoms of hyperglycemia present

- A1C > 10%

- blood glucose levels >300 mg/dL

Timeline for adding agents if not at blood glucose goal

check/modify treatment every 3-6 months

Metformin glucose lowering efficacy

high

Metformin hypoglycemia risk

no

Metformin weight effects

neutral (potential for modest loss)

Metformin CV effects

neutral

Metformin renal effects

neutral

Metformin MASH effects

neutral

Metformin adverse effects

GI side effects

Metformin clinical considerations

potential for vitamin B12 deficiency

Metformin A1C lowering

very high --> up to 2.4%

MASH (metabolic dysfunction-associated steatohepatitis)

liver disease caused by excess fat

SGLT2i glucose lowering

intermediate to high

SGLT2i hypoglycemia risk

no

SGLT2i weight effects

loss (intermediate)

SGLT2i CV effects

Benefit:

- canagliflozin

- dapagliflozin

- empagliflozin

- ertugliflozin

SGLT2i renal effects

Benefit:

- canagliflozin

- empagliflozin

- dapaglifozin

SGLT2i MASH effects

unknown

SGLT2i adverse effects

- DKA risk in people w/ insulin deficiency

- genital mycotic infection

- urosepsis and pyelonephritis

- necrotizing fasciitis in perineum

SGLT2i clinical considerations

intravascular volume depletion --> keep an eye on BP and volume status

SGLT2i A1C lowering

intermediate to high --> 0.5-1%

GLP-1 RA glucose lowering

high to very high

GLP-1 RA hypoglycemia risk

no

GLP-1 RA weight effects

loss (intermediate to very high)

GLP-1 RA CV effects

Benefit: semaglutide SQ

GLP-1 RA renal effects

Benefit:

- dulaglutide

- liraglutide

- semaglutide

GLP-1 RA MASH effects

Benefit: semaglutide

GLP-1 RA adverse effects

GI side effects

GLP-1 RA clinical considerations

- thyroid C-cell tumors BBW

- discontinuation prior to surgery

- pancreatitis

- gallbladder disease

GLP-1 RA A1C lowering

high to very high --> 0.8-1.5%

GIP + GLP-1 RA glucose lowering

very high

GIP + GLP-1 RA hypoglycemia risk

no

GIP + GLP-1 RA weight effects

loss (very high)

GIP + GLP-1 RA CV effects

Benefit: tirzepatide

GIP + GLP-1 RA renal effects

potential benefit

GIP + GLP-1 RA MASH effects

potential benefit

GIP + GLP-1 RA adverse effects

GI side effects

GIP + GLP-1 RA clinical considerations

- thyroid C-cell tumors BBW

- discontinuation prior to surgery

- pancreatitis

- gallbladder disease

GIP + GLP-1 RA A1C lowering

very high --> up to 2.4%

DPP-4i glucose lowering

intermediate

DPP-4i hypoglycemia risk

no

DPP-4i weight effects

neutral

DPP-4i CV effects

neutral (potential risk = saxagliptan)

DPP-4i renal effects

neutral

DPP-4i MASH effects

unknown

DPP-4i adverse effects

joint pain

DPP-4i clinical considerations

potential to cause pancreatitis

DPP-4i A1C lowering

intermediate --> 0.5-0.9%

Pioglitazone glucose lowering

high

Pioglitazone hypoglycemia risk

no

Pioglitazone weight effects

gain

Pioglitazone CV effects

increased risk

Pioglitazone renal effects

neutral

Pioglitazone MASH effects

potential benefit

Pioglitazone adverse effects

- increased risk of HF and fluid retention

- bone fractures

Pioglitazone clinical considerations

bladder cancer

Pioglitazone A1C lowering

high --> up to 1.5%

Sulfonylureas glucose lowering

high

Sulfonylureas hypoglycemia risk

yes

Sulfonylureas weight effects

gain

Sulfonylureas CV effects

neutral

Sulfonylureas renal effects

neutral

Sulfonylureas MASH effects

unknown

Sulfonylureas adverse effects

hypoglycemia

Sulfonylureas clinical considerations

FDA warning on increased risk of CV mortality

Sulfonylureas A1C lowering

high --> 1.5-2%

Insulin glucose lowering

high to very high

Insulin hypoglycemia risk

yes

Insulin weight effects

gain

Insulin CV effects

neutral

Insulin renal effects

neutral

Insulin MASH effects

unknown

Insulin adverse effects

- injection site rxns

- hypoglycemia

Do we initiate basal or mealtime bolus insulin first in T2DM?

basal/bedtime NPH insulin

Initiation of basal insulin in T2DM

start 10 units per day or 0.1-0.2 units/kg per day

Titration of basal insulin in T2DM

increase 2 units every 3 ays to reach fasting plasma glucose goal w/o hypoglycemia