Diabetes Non Insulin Therapy

BG elevation in diabetes due to

• Decreased insulin secretion 

• Decreased insulin sensitivity

• Or Both

Insulin

• Opposite effect of glucagon

• Produced by beta cells

• Stores excess glucose as fat or glycogen

Glucagon

• Produced by alpha-cells

• Releases glucose from glycogen

• Signals fat cells to make ketones when glycogen is depleted

Complications of Diabetes:

Microvascular Diabetes

• Retinopathy

• Diabetic kidney disease

  • Nephropathy 

• Autonomic neuropathy

  • Erectile dysfunction

  • Gastroparesis

  • Urine incontinence

• Peripheral neuropathy

  • Loss of sensation

  • Foot infections 

Complications of Diabetes:

Macrovascular Diabetes

• Peripheral artery disease (PAD)

• Coronary artery disease (CAD)

  • MI

  • Unstable angina

• Cerebrovascular diseases (CVA)

  • Stroke 

  • TIA

T1DM

• Autoimmune destruction of beta-cells in the pancreas

• Insulin cannot be produced once beta-cells are destroyed

• Glucose cannot enter the muscle cells without insulin

In T1DM your body goes into starvation leading to…

• Metabolizes fat into ketones (acidic)

• Ketones used as alternative energy source

• Very high ketone levels leads to diabetic ketoacidosis (DKA)

What test is used to determine if a person is still producing insulin?

C-peptide test

T2DM

Most common (95% of cases)

• Caused by both:

  • Insulin resistance (decreased insulin sensitivity

  • Insulin deficiency

• Pancreatic beta-cells produce less insulin

• Strongly associated:

  • Family history

  • Physical inactivity

  • Obesity

  • Medications

Babies born to mothers with hyperglycemia:

• Larger than normal (macrosomia)

• Higher risk for obesity

• Higher risk for diabetes

BG goals during pregnancy are more stringent

• Lifestyle modifications (diet and exercise)

• Insulin preferred if medication needed

Diabetes Modifiable Risk

• Physical inactivity

• Overweight (BMI ≥25)  

  • BMI ≥ 23 in Asian-American

• History of gestational diabetes

• A1C ≥ 5.7%

• Smoking history

• Hypertension 

  • BP ≥ 140/90 mmHg

  • Taking BP medications

• Dyslipidemia

  • HDL < 35 mg/dL

  • TG > 250 mg/dL

Diabetes Non-Modifiable Risk

• Race or ethnicity

  • Asian American

  • African American

  • Native American/Pacific Islander

  • Latino/Hispanic American

• First degree relative with diabetes

  • Parent

  • Sibling

• CVD history

• Conditions causing insulin resistance

  • Acanthosis nigricans

  • Polycystic ovarian syndrome (PCOS)

  • Thyroid disorders

  • Celiac disease

Diabetes Diagnostic test

A1C (%): ≥ 6.5%, Fasting plasma glucose (FPG): ≥ 126 mg/dL, Oral glucose tolerance test (OGTT): 2-hour plasma glucose ≥ 200 mg/dL.

Prediabetes Diagnostic test

A1C (%): 5.7% to 6.4%, Fasting plasma glucose (FPG): 100 to 125 mg/dL, Oral glucose tolerance test (OGTT): 2-hour plasma glucose 140 to 199 mg/dL.

Diabetes Treatment Goals:

Non-pregnant

a1c<7, preprandial 80-130, 2 hr postprandial <180

Diabetes Treatment Goals:

Pregnant

preprandial ≤95, 2 hr postprandial ≤120

Treatment of T2DM for patients with ASCVD, Heart Failure, or CKD?

Start GLP-1 agonist or SGLT2-inhibitors

If A1C is 8.5-10%

strt 2 drugs at baseline

When is insulin prescribed? T2DM

A1C > 10% or BG ≥ 300 mg/dL

If A1C remains above goal

• Add medications

• Continue until A1C goal is met

A1C Lowering:

Biguanides

1-2%

A1C Lowering:

GLP-1 and GIP Receptor Agonists

0.5-1.5%

Suffix/Prefix:

GLP-1 and GIP Receptor Agonists

-glutide

A1C Lowering:

SGLT-2 inhibitors

0.7-1%

Suffix/Prefix:

SGLT-2 inhibitors

-glifozin

Suffix/Prefix:

Sulfonylureas

Gli-

A1C Lowering:

Sulfonylureas

1-2%

A1C Lowering:

Meglitinides

0.5-1.5%

Suffix/Prefix:

Meglitinides

-glinide

Suffix/Prefix:

DPP-4 Inhibitors

-gliptin

A1C Lowering:

DPP-4 Inhibitors

0.5-0.8%

A1C Lowering:

TZDs

0.5-1.4%

Suffix/Prefix:

TZDs

-glitazone

Biguanides MOA

• Decreases blood glucose via THREE mechanisms:

  • Decreasing hepatic glucose production

  • Decreasing intestinal absorption of glucose

  • Increasing insulin sensitivity

Brand Name:

Metformin

Glucophage, Glucophage XR, Fortamet, Glumetza, Riomet

Metformin IR Dose

500 mg daily or BID

Metformin ER Dose

500 mg - 1000 mg daily

Metformin Max Dose

2000 mg - 2550 mg daily

Metformin Black Box Warning

Risk of lactic acidosis, especially in renal impairment.

Metformin Contrainidcations

eGFR < 30 mL/min/1.73m

cute or Chronic Metabolic Acidosis

Metformin AE

• GI Effects

  • Diarrhea

  • Nausea

  • Flatulence

  • Cramping

• Metallic Taste

Metformin Warnings

• Vitamin B-12 Deficiency

• Not recommended to START in eGFR 30-45

Metformin Counseling

• Monitor B-12 levels 

• Take with meals to decrease GI effects

• Titrate dose to decrease GI effects

• ER form may leave a ghost shell 

Metformin Interactions

Contrast dye, excessive alcohol and topiramate can increase the risk of metabolic acidosis

SGLT-2 inhibitors MOA

Blocks the SGLT-2 in the proximal renal tubules which reduces reabsorption of glucose and increases urinary glucose excretion. 

Brand Name:

Canagliflozin

Invokana

Brand Name:

Dapagliflozin

Farxiga

Brand Name:

Empagliflozin

Jardiance

Brand Name:

Bexagliflozin

Brenzavvy

Invokana Dosing

100 mg PO daily; Can increase to 300 mg/d

Farxiga Dosing

5 mg PO daily; Can increase to 10 mg/d

Jardiance Dosing

10 mg PO daily; Can increase to 25 mg/d

Brenzavvy Dosing

20 mg PO daily

SGLT-2 Inhibitors Contraindications

dialysis

SGLT-2 inhibitors AE

• UTI and Mycotic infections

• Ketoacidosis

• Hypotension

• AKI

• Fractures

• Polyuria

• Polydipsia

SGLT-2 Inhibitors Counseling

• Increased risk of UTIs due to MOA

• Cardiovascular and renal benefits(ASCVD, HF and CKD) specifically:

  • Canagliflozin

  • Dapagliflozin

  • Empagliflozin

• Can cause some weight loss 

• KL is a 10-year-old girl who is seen in the clinic with recent weight loss despite an increased appetite. She has been urinating more often, is thirstier than usual and is lethargic. Her weight is currently in the 40^th percentile for her age. A serum blood glucose is 340 mg/dL and a urinalysis is positive for glucose and ketones. What is the most likely cause of this patient’s symptoms?

• A. Autoimmune destruction of pancreatic myotic cells

• B. Autoimmune destruction of pancreatic alfa cells

• C. Autoimmune destruction of pancreatic c-peptide

• D. Autoimmune destruction of pancreatic beta cells

• D.  Autoimmune destruction of pancreatic beta cells

GLP-1 and GIP RA MOA

• analogs of the incretin hormone GLP-1 which:

  • Increases glucose dependent insulin secretion

  • Decreases glucagon secretion

  • Slows gastric emptying

  • Improves satiety 

Brand Name:

Liraglutide

Victoza (T2DM)

Saxenda (Obesity)

Brand Name:

Dulaglutide

Trulicity (T2DM)

Brand Name:

Semaglutide

Ozempic or Rybelssus{oral} (T2DM)
Wegovy (Obesity)

Brand Name:

Exenatide IR and Exenatide ER

Byetta (IR) and Bydureon (ER) (T2DM)

Brand Name:

Tirezpatide

Mounjaro

Victoza Dosing

0.6 mg SC daily for 1 week, then 1.2 mg SC daily for 1 week, 

Max: 1.8 mg SC daily

Trulicity Dosing

0.75 mg SC weekly for 4 weeks, then can increase to 1.5 mg SC weekly

Ozempic Dosing

0.25 mg SC weekly for 4 weeks, then 0.5 mg SC weekly. Max dose 2 mg SC weekly

Rybelssus Dosing

3mg PO daily for 30 days then 7 mg daily; Max dose 14 mg daily

Byetta Dosing

5mcg SC BID for 1 month

Bydureon Dosing

2 mg SC once weekly

Mounjaro Dosing

2.5 mg SC weekly

What drug shouldn’t be used with DPP-4 inhibitors?

GLP-1 receptor agonists

Which GLP-1 RA have CV benefits?

Semaglutide

Dulaglutide

Liraglutide

How should Reblessus be taken?

Take dose at least 30 minutes before first food/drink/medications of the day

TP is a 56-year-old female with T2DM and GERD who comes to the primary care clinic for her 6-month follow-up visit. She states that she has been experiencing “numbness” and “tingling” in her legs and feet recently. She has also had trouble falling asleep and is worried because she is becoming “forgetful”

Medications:

Glucophage 1000 mg PO BID

Protonix 40 mg PO daily

Which of the following tests should be ordered based on TP’s symptoms?

1. Serum folic acid level

2. Serum vitamin B12 level

3. Serum lipase level

4. Serum C-peptide level

Serum vitamin B12 level

DPP-4 Inhibitors MOA

Prevent the enzyme dipeptidyl peptidase 4(DPP-4) from breaking down the incretin hormones GLP-1 and GIP. Prolongs the BG regulating effects of these hormones

Brand Name:

Sitagliptin

Januvia

Brand Name:

Linagliptin

Tradjenta

Brand Name:

Saxaglitpin

Onglyza

Brand Name:

Alogliptin

Nesina

Januvia Dosing

100 mg PO daily

Tradjenta Dosing

5 mg PO daily

Onglyza Dosing

2.5-5 mg PO daily

Nesina Dosing

25 mg PO daily

DPP-4 Warnings

Pancreatitis

Severe arthralgia

AKI

Risk of HF

DPP-4 AE

Nasopharyngitis

URTIs

Peripheral Edema

DPP-4 inhibitors Counseling

Do NOT use with GLP-1 RAs

Low hypoglycemic risk

Linagliptin is the only one with NO renal adjustments 

TZD MOA

Peroxisome proliferator-activated receptor gamma (PPAR÷) agonists that increase peripheral insulin sensitivity. This then increases the uptake and utilization of glucose by the peripheral tissues

Brand Name:

Pioglitazone

Actos

Actos Dosing and Max Dose

15-30 mg Po daily

Max Dose: 40 mg PO daily

DPP-4 Inhibitors BBW

Can cause or exacerbate HF

TZDs Contraindications

NYHA Class III/IV Heart Failure

TZDs AE

• Edema

• Fractures

• Hepatotoxicity

• Weight Gain

• Increased risk of bladder cancer

• Myalgia

• URTIs

TZDs Counseling

• Benefit in nonalcoholic steatohepatitis

• Major substrates of CYP2C8, use with caution with CYP2CY8 inducers or inhibitors

  • Rifampin (inducer)

  • Gemfibrozil (inhibitor)

• Low hypoglycemic risk

GM is a 65-year-old female who was discharged from the hospital two days ago after experiencing an ischemic stroke. She is at her primary care provider’s office today for a follow-up appointment post-discharge. She was also newly diagnosed with T2DM while hospitalized

Medications:

Plavix 75 mg PO daily

Bufferin 81 mg Po daily

Lipitor 80 mg PO daily

Diovan 80 mg PO daily

Which of the following medications should be added to the patient’s regimen to provide mortality benefit”

1. Januvia

2. Trulicity

3. Levemir

4. Actos

Trulicity

Sulfonylureas MOA

Stimulate insulin secretion from the pancreatic beta cells to decrease blood glucose 

Sulfonylureas Contraindications

Sulfa allergey

Brand Name:

Glipizide

Glucotrol, Glucotrol XL, Glipizide XL

Brand Name:

Glimepride

Amaryl

Brand Name:

Glyburide

Glynase