Copy - GENIAL PRESENTATION

Diabetes Medications Devices and Pumps

Cassie Shields, PharmD, BCACP, CDCESSalina Family Healthcare Center Janaury 18th, 2024

Diabetes Medication Outline

Insulin Therapy

Prevalence

Pathophysiology

Self-Monitoring

Glycemic Goals and Targets

Continuous Glucose Monitoring

Pharmacologic Approaches

Insulin Pumps

Summary and References

Non-Insulin Drug Classes

01

Prevalence ofDiabetes

Fast Facts on Diabetes

50%A1c>7%

89%Overweight

38 Million11.6%

37%CKD

$1 in $7spent on diabetes

22%Tobacco Users

70%BP not at goal (<140/90)

CV Risks and Diabetes

2-5x

41%

66%

20% Heart Attacks13% Strokes

2-5x Risk of developing HF in pts with T2D

Stage 3 or 4 CKD

2 out of 3 people with diabetes or prediabetes die of heart disease or stroke

27% of End-Stage Renal Disease due to diabetes as a primary cause. 62,000 new cases/year

60-80% increase risk of death from CV causes in pts with HF and T2D

We love data

02

Pathophysiology ofDiabetes

Inzucchi SE, Sherwin RS. Type 2 diabetes mellitus. In: Goldman L, Schafer AL, eds. Goldman’s Cecil Medicine. 24th ed. Philadelphia, PA: Saunders (Elsevier); 2011:chap 267.

03

Glycemic Goal and Treatment

A1c and Average Blood Glucose

Goals of Therapy

Individual Goals + Guidelines Goals

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

Pharmacologic Approaches to Glycemic Treatment

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

04

Non-Insulin DrugClasses

Biguanides

MOA: Decreases hepatic gluconeogenesis and stimulates glucose uptake by the tissues

Dose (Oral)

Starting: 500mg ER daily 1,000mg ER daily 1,000mg ER BID -TAKE WITH FOODTarget Dose: 2,000mg ER daily

Side-Effects

GI (diarrhea, nausea)B12 Deficiency (need supplementation if taking >12 months) Lactic Acidosis (Rare and monitor in kidney dysfunction and age)

Key Take Aways/Precautions/Contraindications

-eGFR: <45mL/min: decrease dose by half-eGFR<30mL/min: Stop/Do not initiate -Caution in >80 Years of Age -Lowers A1c 1-1.5% (initial therapy)

Sulfonylureas

MOA: Stimulates pancrease to release more insulin Drugs in this Class: Glyburide, Glimepiride, Glipizide (2nd generation)

Dose (Oral)

Starting: Daily to BID (Take with largest meal of day) -TAKE WITH FOODTarget Dose: Glipizide 40mg daily (most common and safe sulfonylurea)

Side-Effects

HYPOGLYCEMIA Weight Gain (4-6 lbs)

Key Take Aways/Precautions/Contraindications

Highest to lowest hypoglycemia risk: Glyburide>Glimepiride>Glipizide-Avoid taking with insulin (increased hypoglycemia risk) ***Caution in elderly d/t fall risk (Beer's List) -Targets post-prandial blood sugars Ave A1c lowering 0.8%

Thiazolidinediones (TZDs)

MOA: Increase insulin sensitivity in muscle and fat Drugs in this Class: Pioglitazone and Rosiglitazone

Dose (Oral)

Target Dose for Pioglitazone: 15-45mg daily

Side-Effects

Weight Gain (8lbs) Edema Upper Respiratory Infections

Key Take Aways/Contraindications

AVOID IN Heart FailureIncrease risk for Bone Fractures Increase Risk for Bladder Cancer Good Evidence for using in MASLD/MASH (metabolic associated steatotic liver disease/metabolic associated steatohepatitis)-Targets Fasting blood sugars Ave A1c lowering 0.8%

Dipeptidyl Peptidase IV inhibitors (DPP-4i)

MOA: inhibits DPP-4 enzyme responsible for degrading incretin hormones GLP-1 and GIP Drugs in this Class: Alogliptin, Linagliptin, Saxagliptin, Sitagliptin "The GLIPTINs"

Dose (Oral)

Starting: Daily Target Dose: Glipizide 40mg daily (most common and safe sulfonylurea)

Side-Effects

Nasopharyngitis, URI, Headache

Key Take Aways/Precautions/Contraindications

Kidney Adjustments for sitagliptinNO renal adjustments for linagliptin, but DDI with CYP3A4 AVOID Saxagliptin in HF AVOID ALL DPP-4i if past hx of pancreatitis or develop bullous pemphigoidAve A1c lowering 0.5-0.7%

Glucagon Like Peptide Receptor Agonists (GLP-1 RA)

MOA: mimics/activates GLP-1 receptor sites to stimulate relase of insulin after eating, inhibit glucagon and slow glucose absorption into the bloodstream Drugs in this Class: Dulaglutide, Exenatide, Liraglutide, Semaglutide

Dose (Oral or SC)

Target Dose: Semaglutide (oral) 14mg daily, Semaglutide (SC) 2mg wkly Liraglutide 1.8mg SC daily, Dulaglutide 4.5mg SC wkly, Exenatide SC 2mg wkly

Side-Effects

GI (N/V/D)-slower titration if experience or try different drug in class

Key Take Aways/Precautions/Contraindications

Avoid in Pancreatitis hx, MTC, C-Cell Tumors, MEN Caution in gastroparesis Evaluate for gallbladder disease if Cholecystitis No renal adjustments neededAve A1c lowering 1.5-2%

Dual GIP (Glucose-dependent insulinotropic polyeptide)/GLP-1 RA

MOA: agonizes GIP (induces insulin secretion to facilitate metabolism of COOH, Fats, Proteins. Agonizes GLP-1 in response to elevated BG, decrease glucagon secretion and delay gastric emptying Drugs in this Class: Tirzepatide

Dose (SC)

Starting Dose: 2.5mg weekly, double dose every 4 weeks Target Dose: Tirzepatide 15mg weekly

Side-Effects

GI (N/V/D) Hypoglycemia risk if taken with insulin

Key Take Aways/Precautions/Contraindications

Avoid in Pancreatitis hx, MTC, C-Cell Tumors Avoid in gastroparesis Decreases concentration of oral contraception pills (OCPs) when titrating tirzepatide Ave A1c lowering 1.5-2%

GLP Order of Preference (Effectiveness)

Selective Sodium-Glucose Transporter-2 (SGLT-2) Inhibitor

MOA: inhibits expression of SGLT-2, which is found in proximal renal tubules and is responsible for filtered glucose reabsorption. Increase urinary glucose excretion Drugs in this Class: Bexagliflozin, Canagliflozin, Dapagliflozin, Empagliflozin, Ertugliflozin

Dose (oral)

Starting Dose: lowest dose daily in AM x90 days -recheck BMP (to ensure SCr WNL). Target dose: max dose

Side-Effects

UTI Mycotic injections Nasopharyngitis

Key Take Aways/Precautions/Contraindications

Euglycemic DKA Caution in starting if BGs are extremely elevated (precipitates more side-effects) Consider decreasing loop diuretic dose when initiating to avoid volume depletion Fournier gangreneAve A1c lowering 1.5-2%

Major Side-Effects and Contraindications

Other Drug Classes

Alpha Glucosidase Inhibitors-blocks enzymes that digest starches in stomach and intestine; take with a mealAcarbose Miglitol

Metglitinides-increase insulin production; take with a mealNateglinide Repaglinide

Bile Acid Sequestrant-decreases glucose level by increasing incretin secreation through intestineColesevelam

Dopamine-2 Agonist-used in insulin resistance to reset abnormally elevated hypothalamic drive for increased plasma glucoseBromocriptine

Amlyn mimetic-inhibits glucagon secretion, delays gastric emptying and helps with satietyPramlintide

Safety of Diabetes Medications

Cardiovascular Outcomes Trials (CVOTs)All new diabetes medication to demonstrate "no harm"

2008

3-Point MACE endpoint

Major Adverse Cardiovascular EventTrial lenth at least 2 years with 95% CI for non-inferiority

3 Categories for Trials

-CV Death-Non-fatal MI -Non-fatal Ischemic Stroke

Pharmacologic Approaches to Glycemic Treatment

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

Pharmacologic Approaches to Glycemic Treatment

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

05

The Wide World of Insulin

1922

Invention of Insulin

History of Insulin

1938

Insulin approved by FDA

1982

Synthetic human insulin approved. Humulin by Eli Lilly

19962000

HumalogLantus

2009/2021

Biologics Price Competition and Innovation Act

https://www.fda.gov/about-fda/fda-history-exhibits/100-years-insulin

Physiologic Compenents of Insulin

https://www.uspharmacist.com/article/insulin-analogs-what-are-the-clinical-implications-of-structural-differences

Physiologic Compenents of Insulin

https://www.uspharmacist.com/article/insulin-analogs-what-are-the-clinical-implications-of-structural-differences

Types of Insulin

Other Types of Insulin

Types of Insulin

3. Intermediate(NPH)

1. Rapid-ActingMeal-Time Bolus

4. Long-Acting (Basal) Ultra Long Acting

2. Short Acting (R)

Decreases fasting glucose Requires consistent insulin levels 50% of daily insulin needs

Available in U100 and U500 u500 used for patients with insulin resistance using 200 units or more of insulin/day

Significant impact in gestational diabetes requiring insulin

Limits postprandial hyperglycemia, corrects BGs when not at goal Each meal requires 10-20% of total insulin needs

Hypoglycemia

Symptoms

Sweating/Shaking, Heart palpitations, tachycardia, hunger, headache, dizzy/light headedness, weird dreams, confusion, blurry vision, weak/extreme tiredness, difficulty speaking, syncope, coma, death

Rule of 15s

Correct with 15-20gm of simple carbs every 15 min until stable or BG >/= 100mg/dL

Glucagon

Glucagon Injection 1mgBaqsimi 3mg (nasal)GVOKE 1mg (pen)

06

Monitor

What is a CGM?

Continuous Glucose Monitor

-Continously gives glucose readings every 1-5 min 288+ glucose readings/day

How does it work

A sensor is inserted under the skin and measures level of glucose in the interstitial fluid every 10 seconds and changes it into an electrical signal. A transmitter sends the signal to the monitor, which records the glucose value. Every 1-5 minutes an average glucose value is given on the monitor.

3 Basic Parts

SensorTransmitter Receiver/Reader

Why use a CGM?

Limitations of A1c

Anemia, Ethnicity, Pregnancy, sickness, medications, hypoglycemia, ESRD

Decreases Hypoglycemia

Amount of time with low BGs by 43%

Lowers MicrovascularComplications

Decrease Retinopathy Risk by 64% Decrease Microalbuminuria by 40%

Glucometer vs CGM

Glucometers are necessary in monitoring for diabetes. Glucometers are also necessary to address immediate symptoms in acute situations, regardless of a CGM.

Types of CGMs

American Diabetes Association. 7. Diabetes technology: Standards of Medical Care in Diabetes-2021. Diabetes Care 2021;44(suppl. 1): S88.

CGM Report

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

CGM Terminology

American Diabetes Association. 7. Diabetes technology: Standards of Medical Care in Diabetes-2021. Diabetes Care 2021;44(suppl. 1): S88.

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

CGM Comparison

Standards of Care in Diabetes—2024. Diabetes Care 1 January 2024; 47 (Supplement_1): S111–S125

Freestyle Libre

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

Dexcom

G6 G7

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

Medtronic Guardian

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

Senseonics Eversense

Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006

07

Insulin Pumps

Insulin Pumps

What is an Insulin Pump?

-small wearable device that delivers rapid-acting insulin every few minutes 24 hours a day-programmed to deliver insulin based on weight, total daily dose of current insulin, other needs

How do they deliver insulin?

-Requires training with a certified pump trainer -A reservoir holds up to 3mL of insulin. Then it pumps insulin through a tube connected to a cannula under the skin to deliver the calculated insulin dose at the specific desired rate

Types of Pumps

A) Patch/Micro Insulin Pumps Sticks directly onto the skin and need changed every 3 daysB) Tethered insulin pump (pumps with tubing) Attached through tube, cannula and/or needle (infusion sets)

https://jdrf.org.uk/knowledge-support/managing-type-1-diabetes/guide-to-type-1-diabetes-technology/insulin-pumps/

4 Types of Insulin Pumps

https://www.pantherprogram.org/device-comparison-chart

In Summary...

• Several diabete drug classes
• Diabetes medications are COMPLEX
• Require an understanding of underlying condition
• Cool Technology to help control diabetes and prevent complications

08

References

1. CDC National Diabetes Statistics Report 2020. Accessed January 4th, 2024 2. Inzucchi SE, Sherwin RS. Type 2 diabetes mellitus. In: Goldman L, Schafer AL, eds. Goldman’s Cecil Medicine. 24th ed. Philadelphia, PA: Saunders (Elsevier); 2011:chap 267. 3. Diabetes Care. 2023;47(Supplement_1):S111-S125. doi:10.2337/dc24-S006 4. Medscape https://emedicine.medscape.com/article/117853-medication 5. https://www.fda.gov/about-fda/fda-history-exhibits/100-years-insulin 6. https://www.uspharmacist.com/article/insulin-analogs-what-are-the-clinical-implications-of-structural-differences 7. American Diabetes Association. 7. Diabetes technology: Standards of Medical Care in Diabetes-2021. Diabetes Care 2021;44(suppl. 1): S88. 8. https://jdrf.org.uk/knowledge-support/managing-type-1-diabetes/guide-to-type-1-diabetes-technology/insulin-pumps/

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