DM part 1 Flashcards
Key Players in Glucose Hemostasis
Glucose homeostasis:
Glucose:
Insulin:
Pancreatic Islet Hormones (endocrine);
Key Players in Glucose Hemostasis
Glucose homeostasis: balance between hepatic glucose
production and peripheral glucose uptake and utilization
Glucose – source of energy
Insulin - most important regulator of glucose/metabolic
equilibrium
Pancreatic Islet Hormones (endocrine)
◦ Maintains glucose balance
◦ 4 types of peptide-secreting cells
Beta (B) – secrete insulin
Alpha (A) – secrete glucagon
Delta (D) – secrete somatostatin
PP (also known as gamma) – secrete pancreatic polypeptide
Relationship between Glucose and Insulin
Glucose is the main factor controlling synthesis and secretion of insulin
Two ways insulin is released:
◦ Steady basal release of insulin
◦ Response to increased glucose
About 1/5 of insulin stored in the pancreas of an adult is secreted daily
Glucose-Insulin Roller Coaster diagrammed
Glucose stimulated insulin secretion
- Glucose transported by glucose transporter into beta cell
- Metabolism alters ion channel (Ca 2+) activity leading to insulin secretion
- Incretin hormones: glucagon-like peptide 1 (GLP1) and glucose - dependent insulinotropic polypeptide (GIP) released by cells in the small intestines after food ingestion, stimulate insulin secretion when the blood glucose is above the fasting level
Diabetes Mellitus (DM)
A group of complex chronic metabolic disorders characterized by high blood glucose concentrations (hyperglycemia)
◦ Insulin deficiency
◦ Often combined with insulin resistance
◦ Abnormalities in the metabolism of carbohydrates, proteins, fats and insulin.
Hyperglycemia can be due to:
◦ Uncontrolled hepatic glucose output
◦ Reduced uptake of glucose by skeletal muscle
◦ Reduced glycogen synthesis
Type 1 (T1DM)
◦ Absolute deficiency of insulin resulting from autoimmune destruction of pancreatic B
cells = insulin deficiency
◦ Commonly occurs in childhood and adolescence.
◦ Without insulin treatment patients will ultimately die of diabetic ketoacidosis
Type 2 (T2DM)
◦ Hyperglycemia due to insulin resistance (proceeds overt disease) + progressive loss of
insulin secretion
◦ May have normal, increased (hyperinsulinemia) or decreased insulin levels due to
abnormal beta cell function
◦ Most commonly presents in adulthood and in obese patients
◦ Managed with diet, oral/subcutaneous (SC) antidiabetic agents and insulin SC
◦ Accounts for ~ 95% of individuals with diabetes > 30 years
◦ Alarming increases T2DM in obese children and adolescents
◦ Can be delayed or prevented with lifestyle modifications – diet, physical activity and
weight control
other DM forms
gestational diabetes, medications - glucocorticoids
CLINICAL PRESENTATION of DM
- Symptoms may include polydipsia, polyphagia, polyuria, nocturia, blurred vision. (More common on type 1/ occurs in varying degree in Type 2 DM).
- Type 1 DM often associated with weight loss, ketoacidosis (dehydration)
- Majority of Type 2 patients are asymptomatic and diagnosed by laboratory testing
Screening for T2DM and Prediabetes in Asymptomatic
Patients
The ADA’s guidelines recommend screening for prediabetes and
T2DM through an informal assessment of risk factors or with a
validated assessment tool to help physicians determine whether
a diagnostic test is appropriate for a patient.
The guidelines provide an example of an approved assessment
tool: ADA’s Risk Test.
DM increasing prevalence
Increasing aging population and numbers of overweight adolescents, teenagers and adults = rapid increases in prevalence
Lab tests for diagnosis and monitoring of diabetes (WNL, PreDM and DM)
Spectrum of normal glucose to diabetes
Systemic Complications of DM
Macrovascular
◦ Brain
◦ Heart
◦ Extremities (peripheral vascular disease)
Microvascular
◦ Eyes
◦ Kidney
◦ Nerves; Peripheral and Autonomic
◦ Periodontal disease
Glycemic Goals of DM tx
ndividualizing Glycemic Targets
Additional DM Goals – Risk Reduction Strategies
vascular
Reduce the risk of macrovascular and microvascular (and other)
complications through glycemic control and controlling co-morbid conditions to which DM contributes
Additional DM Goals – Risk Reduction Strategies
CV
Reduce cardiovascular risk factors
Control BP
Control lipids
Smoking Cessations
Additional DM Goals – Risk Reduction Strategies
vaccines
Reduce the risk of vaccine-preventable diseases
Immunizations
Examples: Flu, Tdap/Td, Pneumococcal, Hepatitis B (others
Additional DM Goals – Risk Reduction Strategies
periodontal
Minimize periodontal complications due to diabetes mellitus,
provide safe and effective dental care and promote good oral
health
Non-pharmacologic therapy for DM
Medical Nutrition Therapy
Physical Activity
Medical Nutrition Therapy for DM
◦ Focus on carbohydrates for glycemic management
Typically stay between 3-4 carbohydrate choices or 45-60 grams of carbohydrate per meal
Eat 3 meals or 5 smaller meals throughout day If numeracy skills are low, may use plate method
Physical Activity for DM
◦ Helps body regulate glucose and decreases insulin resistance
◦ Lowers BP, cholesterol, stress, weight
◦ Amount
150 min of moderate-intensity spread over at least 3 days and no more than 2 consecutive days without
Resistance training 2x per week
insulin hx
History of insulin in the treatment of diabetes = interesting
◦ Insulin destroyed in GI tract
◦ Before insulin therapy Type I DM = death sentence (wasting and
dying from ketoacidosis)
◦ Breakthrough in 1920’s when insulin was isolated
Noble Prize = Banting and Best (University of Toronto)
insulin soruces
Porcine or Bovine sources
Bovine - discontinued in US in1978
Porcine manufactured in US until 2005
◦ Significant variability between batches
insulin allergies
immune response to animal-based products
Current Insulin therapy
form?
bath variability?
Modified amino acid sequences?
◦ Differences in?
◦ Categorized by?
Recombinant human insulin (made by recombinant
DNA-rDNA technology)
Avoid batch variability and allergies from animal sources
Modified amino acid sequences (insulin analogs)
provide rapid/short acting and long acting/basal
insulins
◦ Differences in timing to peak effect and duration
◦ Categorized by their onset or action
Rapid-acting Insulin
Rx?
Appearance-?
form?
Rx only
Appearance- clear/colorless
rDNA – human insulin analogs
Rapid-acting Insulin names
insulin lispro, aspart, and glulisine
LAG
insulin lispro onset/peak/duration
insulin aspart onset/peak/duration
insulin guisiline onset/peak/duration
meal timings with rapid insulins
given within 10-15 minutes before or up to 20 minutes after
rapid insulins compatability
NPH
Short-acting (Regular) Insulin
Rx?
Appearance?
form?
Non-Rx – 100 units/ml (Humulin R U-500 - RX)
Appearance- clear/colorless
rDNA – human insulin analogs
short acting insulin names
Humulin R
Novolin R
onset/peak/duration Humulin R
onset/peak/duration Novolin R
short acting insulin meal timings
30 min before
compatability of short acting insulins
NPH
Inhaled Insulin - Afrezza
rate? given with?
route?
Amount of insulin delivered to lungs depends on?
Dosing conversion from?
Contraindicated in ?
Not recommended in?
Risk of ?
cost?
Inhaled Insulin - Afrezza
Rapid acting insulin – given with meals
Oral inhalation
Amount of insulin delivered to lungs
depends on individual factors
Dosing conversion from injected
insulin
Contraindicated in chronic lung
disease (asthma/COPD)
Not recommended in smokers
Risk of bronchospasms and cough
EXPENSIVE!
Intermediate-acting (NPH)Insulin
NPH?
Rx?
Appearance?
form?
NPH - Neutral Protamine Hagedorn
Non-Rx
Appearance - cloudy
rDNA – human isophane insulin suspension
Intermediate-acting (NPH)Insulin names
Humulin N
Novolin N
Humulin N onset/peak/duration
Novolin N onset/peak/duration
Frequency of administration for Humulin N
and Novolin N
SC – usually one to two times a day
Humulin N/ novolin N
compatabilty
Can mix with aspart, glulisine, lispro, and regular insulin
Long-acting Insulin
Rx?
Appearanc?
form?
Rx only
Appearance – clear, colorless
rDNA – human insulin analogs
Long-acting Insulin names
insulin glargine (100units/mL), demetir, glargine (300 units/mL)
onset insulin glargine
1.1hrs
onset insulin demetir
1.1-1.2 hrs
onset of 300 units/mL of glargine
develops over 6hrs
insulin glargine/demetir peak
mo real peak
insulin glargine and demetir duration
insulin glargine/demetir freq of admin
duration of 300units/mL glargine
over24 hrs
freq admin of 300units/mL glargine
SC once daily at the
same time each day.
May take at least 5
days to see maximum
effects
Long-acting Insulin compatabilites
Do not mix with other insulins or dilute
Ultra Long-acting Insulin
Rx?
Appearance ?
form?
Rx only
Appearance – clear, colorless
rDNA – human insulin analogs
Ultra Long-acting Insulin name
insulin degludec (Tresiba)
insulin degludec onset, peak, and duration?
insulin degludec frequency of admin
SC – once daily at any time of day
insulin degludec compatability?
do not mix with other insulins
Summary of Duration of Action of Insulins
why would there be insulin mixtures? when are these given? are there any cons?
Actions of immediate/short and longer acting insulin combined
Typically given pre-breakfast and pre-supper or pre-breakfast, lunch and supper.
Disadvantages in dosing and individualizing therapy – more risk of hypoglycemia
types of insulin pens
- Reusable insulin pen– must load with insulin cartridges - sold separately
- Disposable insulin pens - come filled with insulin and are thrown away when empty
advantages of insulin pens
disadvantages of insulin pens
Basal-bolus regimen of insulin admin
(4 injections total/day)
◦ Mimic physiologic insulin release
Rapid-acting/NPH insulinmix admin
2 injections/day
◦ Rapid or regular insulin mix with NPH
Continuous Insulin Infusion Pumps
growing use in? mechanism? what insulin type used?
Growing use - primarily in T1DM
Deliver exogenous insulin that more closely approximates the normal biologic function and performance of the pancreas
◦ devices only use short- or rapid-acting acting insulin as basal insulin with continuous delivery with bolus administration as needed
Continuous Insulin Infusion Pumps mechanism
Programed external pump - worn continuously
◦ Delivers insulin through a cannula inserted just beneath the surface of the skin
◦ One injection site for 72 hrs
Continuous Insulin Infusion Pumps advantages
◦ Improved glycemic control
◦ Decreased A1c
◦ Decreased risk of hypoglycemia
Continuous Insulin Infusion Pumps monitoring
Many pumps have Continuous Glucose Monitoring (CGM) system integrated
within the pump or they can be used separately
Continuous Insulin Infusion Pumps Adverse Effects:
* Pump failures?
* Mechanical?
* Blockages?
* Infusion sit?
* Instability of?
* User?
* Rates?
* Importance of?
* Infections?
- Pump failures – hyperglycemia or hypoglycemia
- Mechanical failures
- Blockages within the infusion set
- Infusion site complications
- Instability of the insulin stored within the pump
- User error – usually the most common
- Rates declining as technology improves
- Importance of patient education
- Infections at injection site, lipomas
- More expensive than multiple daily injections
Continuous Insulin Infusion Pumps dental implications
Dental: Either Hypo- or Hyperglycemia may occur!
* If pt confused/unresponsive, always push “suspend” button immediately.
* Then check display to assess last glucose trend
Glucose Monitors and Continuous Glucose Monitoring (CGM)
Purpose:
Safety and efficacy?
Purpose: to monitor blood glucose levels in patients with diabetes
Safety and efficacy of insulin and other diabetic drugs
Blood Glucose Meters (many brands)
◦ Finger sticks?
◦ Self-monitoring of Blood Glucose (SMBG)
Frequency of monitoring?
◦ Finger sticks – moment in time
◦ Self-monitoring of Blood Glucose (SMBG)
Frequency of monitoring varies depending on type of diabetes and medications
Occasional to Morning fasting, before meals, before exercise, etc
Continuous Glucose Monitoring (CGM) – stand alone
Compact medical systems that continuously monitor glucose in almost real time
Readings generally at 5-minute intervals
Small sensor with with a cannula is inserted into arm or abdomen – replaces every 10-14 days (secured with adhesive)
Reusable transmitter sends readings wirelessly, usually to phone, computer or other
monitoring device
Alerts can be sent to notify of low or high glucose (or customized) and can share device data with providers, parents, etc.
Used by patients with either T1DM or T2 DM
Insurance coverage varies with T2DM
Use of insulin in DM Type 1
◦ required?
◦ frequency?
◦ dose sizes?
◦ Life-long insulin required along with diet management
◦ Multiple daily injections of prandial insulin and basal insulin or continuous subcutaneous insulin infusion.
◦ Often require lower doses of insulin than Type 2 because less issue with insulin resistance
Use of insulin in DM type 2
◦ Other treatment options?
◦ Approximately what % benefit? all need it?
◦ Often require what doses?
◦ Often start with ?
◦ May add what if glycemic goals not met?
◦ Other treatment options usually implemented first unless severe hyperglycemia
Diet management
Oral anti-diabetic agents
◦ Approximately 1/3 patients (more?) benefit from insulin
Eventually every patient with type 2 DM requires insulin – beta cell failure
◦ Often require higher doses than Type 1 because of insulin resistance
◦ Often start with basal/long-acting insulin and continue certain oral anti-diabetic agents
◦ May add bolus to basal if glycemic goals not met
Insulin Dosing type 1
◦ Generally, the starting insulin dose is based on weight, with doses ranging
from 0.4 to 1.0 units/kg/day of total insulin with higher amounts required
during puberty
Insulin Dosing type 2
◦ most convenient initial insulin regimen, beginning at? depending on?
◦ Many individuals with type 2 diabetes may require?
◦ The recommended starting dose of mealtime insulin is ?
◦ After titration to goals and advancing disease, patients with Type 2 often
require?
◦ Basal insulin alone is the most convenient initial insulin regimen,
beginning at 10 units per day or 0.1–0.2 units/kg/day, depending on the
degree of hyperglycemia.
◦ Many individuals with type 2 diabetes may require mealtime bolus insulin
dosing in addition to basal insulin
◦ The recommended starting dose of mealtime insulin is 4 units, 0.1
units/kg, or 10% of the basal dose
◦ After titration to goals and advancing disease, patients with Type 2 often
require higher doses (unit/kg) than Type 1 because of insulin resistance
Adverse Effects of Insulin
HYPOGLYCEMIA!
◦ Highest risk of any diabetes medication
◦ Tighter control (of glucose) = increased risk of hypoglycemia
hypoglycemia symptoms
symptoms: shaky/tremors, confusion, nervous, sweating, clamminess,
light headed/dizziness, fatigue, sleepiness, agitation, anxiety, hunger,
nausea tingling or numbness (especially of lips and tongue), vision
changes, headache, anger/stubbornness, sadness, tachycardia
◦ Severe hypoglycemia may result in seizures or loss of consciousness
how should we managed suspected hypoglycemia
◦ Manage patient as if hypoglycemic, until proven otherwise
◦ Check blood glucose with monitor
Implications of hypoglycemia for Dental Practice
Implications for Dental Practice: Patients skipping a meal for a dental procedure or even a visit should not take their short/rapid acting insulin dose. Patients who eat normally should take all of their insulin prior to a visit.
Definitions for Hypoglycemia
◦ Not all patients will experience hypoglycemia
Certain antidiabetic drugs and patient risk factors increase risk
◦ Serious, clinically significant: < 54 mg/dL
◦ Glucose Alert Value: < 70 mg/dL
tx of Hypoglycemia
rule? tx if?
Rule of 15s
Treat if < 70 mg/dl
* 15-20 gms fast acting carbs = 3-4 glucose tablets, 4 oz juice or regular soda, 5 lifesavers, 3 peppermints
* Glucose gel also available – follow directions on tube
* If next meal is more than 1 hr away consider a small snack to prevent recurrence or eat meal
* Observe patient 30-60 mins after recovery. Confirm normal glucose level before patient allowed to leave office
* Consider referring patient to physician for follow up
Management of Hypoglycemia
Unconscious patient or unable to swallow
◦ Call 911 (have someone call or if alone call after administering 1st dose of glucagon)
◦ Stimulates gluconeogenesis - release of stored glucose ( glycogen) from the liver.
what is given to hypoglycemic who is unconscious or unable to swallow
◦ 1mg glucagon intravenously or intramuscularly in buttock, arm or thigh (may give IM at almost any body site if necessary). Repeat at 15 minutes if no response
◦ 0.5 mg for pediatrics < 44 lbs
Patient needs glucose after injection
◦ OR, give 50ml of 50% dextrose IV
Turn on side to prevent aspiration
Rx affecting Glucose Production at liver
Biguanides
(Thiazolidinediones)
GLP1 RAs
Rx’s affecting Glucose Absorption at intestine:
a-glucosidase inhibitors
Bile acid sequestrants
GLP1 RAs
Rx’s causing Slowed Gastric Emptying:
Incretin & Amylin mimetics
GLP1-RAs
Rx’s affecting insulin secretion
Sulfonylureas
Meglitinides
Insulin
DPP-4 inhibitors
Incretin mimetic (GLP1-RA)
Glucagon inhibition Rx
Incretin mimetics
DPP-4 Inhibitors
Amylin mimetics
Kidney dm rx
Sodium glucose co- transporter 2 inhibitor
Muscle Peripheral Glucose Uptake inhibitor Rx’s
Thiazolidinediones
Biguanides
GLP1 RAs
Satiety/Feeding rx’s
Incretin mimetics
Amylin mimetics
Dopaminergic
Biguanides moa
Metformin (Glucophage) only available drug in class
MOA
◦ Keeps the liver from releasing too much glucose
◦ decreases Hepatic glucose production (gluconeogenesis – markedly increased in Type 2) – PRIMARY MECHANISM
◦ Decreases insulin resistance (increases insulin sensitivity)- increases glucose utilization in muscle and adipose tissues
◦ Inhibits intestinal absorption of glucose
Metformin
Often a drug of choice in? why? also used in?
Often a drug of choice in Type 2 (especially in obese patients and because of lower costs)
◦ Lower cost
◦ Effective A1C lowering for oral agent
Use in pre-diabetes (decreases risk of progression to DM)
weight gain with metformin
Weight neutral/ameliorates insulin-associated weight gain
hypo risk with metformin as monotherapy
low risk
metformin and GI
how can we help reduce this?
Notable GI adverse drug effects (ADEs) such as diarrhea/loose stools, flatulence, dyspepsia, abdominal distension/pain, nausea/vomiting
◦ Titrating the dose up slowly can help patients tolerate and taking with food can help minimize
◦ Some patients can’t tolerate and must discontinue therapy
XL formulation may cause less GI side effects
what can become def with metformin
Risk of B12 deficiency (should be checked annually)
metabolic ADR of metformin
Rare risk of causing lactic acidosis
◦ watch with dehydration
◦ contraindicated in chronic kidney disease (GFR < 30 ml/min), caution with GFR between 30-45 ml/min)
Glucagon Like Peptide-1 Receptor Agonists
Albiglutide, Dulaglutide, Exenatide,
Liraglutide, Lixisenatide, Semaglutide
Albiglutide, Dulaglutide, Exenatide,
Liraglutide, Lixisenatide, Semaglutide
Glucagon Like Peptide-1 Receptor Agonists
Glucagon Like Peptide-1 Receptor Agonists
Most options available as?
which available sc and po?
Dosing frequency?
Most options available as injections (sc) only
Semaglutide available sc and po
Dosing frequency varies – BID, daily and
weekly depending on medication and formulation
Glucagon Like Peptide-1 Receptor Agonists moa
stimulates GLP-1 receptors in the pancreas to increases insulin secretion in response to elevated glucose. In addition, stimulation of GLP-1 receptors in the GI tract and CNS decrease glucagon secretion and slow gastric emptying
Albiglutide moa
stimulates GLP-1 receptors in the pancreas to increases insulin secretion in response to elevated glucose. In addition, stimulation of GLP-1 receptors in the GI tract and CNS decrease glucagon secretion and slow gastric emptying
Dulaglutide moa
stimulates GLP-1 receptors in the pancreas to increases insulin secretion in response to elevated glucose. In addition, stimulation of GLP-1 receptors in the GI tract and CNS decrease glucagon secretion and slow gastric emptying
Exenatide moa
stimulates GLP-1 receptors in the pancreas to increases insulin secretion in response to elevated glucose. In addition, stimulation of GLP-1 receptors in the GI tract and CNS decrease glucagon secretion and slow gastric emptying
Liraglutide moa
stimulates GLP-1 receptors in the pancreas to increases insulin secretion in response to elevated glucose. In addition, stimulation of GLP-1 receptors in the GI tract and CNS decrease glucagon secretion and slow gastric emptying
Lixisenatide moa
stimulates GLP-1 receptors in the pancreas to increases insulin secretion in response to elevated glucose. In addition, stimulation of GLP-1 receptors in the GI tract and CNS decrease glucagon secretion and slow gastric emptying
Semaglutide moa
stimulates GLP-1 receptors in the pancreas to increases insulin secretion in response to elevated glucose. In addition, stimulation of GLP-1 receptors in the GI tract and CNS decrease glucagon secretion and slow gastric emptying
GLP 1- Receptor Agonists
Benefits
- weight loss
- CV
- renal
GLP 1- Receptor Agonists weight
◦ Weight loss
◦ Higher dosages approved for weight loss
semaglutide (Wegovy) - injection
liraglutide (Saxenda) - injection
GLP 1- Receptor Agonists CV
◦ CV benefits (except lixisenatide and immediate-release exenatide)
Atherosclerotic Cardiovascular Disease (ASCVD)
GLP 1- Receptor Agonists renal
preffered?
◦ Kidney benefits – Chronic Kidney Disease (CKD) (liraglutide, semaglutide) – but SGLT2 preferred
GLP 1- Receptor Agonists ADE’s:
* gi?
* injection?
* panc?
* organ dx?
* * tumors?
nausea, diarrhea, injection site reactions, pancreatitis (rare),
gallbladder disease, risk of Thyroid-C cell tumors
GLP 1- Receptor Agonists ADE’s risk of hypo as monetherapy
Hypoglycemia: low risk with monotherapy (may increase risk in
combination therapy with sulfonylureas/others that cause hypoglycemia)
Glucose-dependent insulinotropic polypeptide (GIP) agonist + Glucagon-like, peptide-1 (GLP-1) agonist (“twincretin”)
approved for? indication?
Tirzepatide (Mounjaro) – FDA approved 2022 for the treatment of adults with type 2 diabetes
◦ Weight management indication
Tirzepatide moa
Glucose-dependent insulinotropic polypeptide (GIP) agonist + Glucagon-like, peptide-1 (GLP-1) agonist (“twincretin”)
increases insulin secretion in response to elevated glucose, decreases glucagon secretion, slows gastric emptying
GIP/GLP-1 Receptor Co-agonist ADE’s:
◦ GI?
◦ Pancreas?
◦ Gallbladder>?
◦ hypo?
◦ thyroid?
◦ GI (e.g., diarrhea, nausea, vomiting)
◦ Pancreatitis (rare)
◦ Gallbladder disease (rare)
◦ Low risk of hypoglycemia when used as monotherapy.
◦ Linked to medullary thyroid cancer in rats
Tirzepatide
GIP/GLP-1 Receptor Co-agonist addt info:
◦ More weight loss than?
◦ More A1c reduction than?
◦ CV/kidney?
◦ Monitor for?
◦ May delay?
◦ More weight loss than GLP-1 agonists
◦ More A1c reduction than most GLP-1 agonists.
◦ No CV or kidney outcomes data yet!
◦ Monitor for retinopathy progression
◦ May delay oral contraceptive absorption
Sodium glucose cotransporter-2 (SGLT2)
inhibitors - MOA
Located in the S1 segment of the proximal renal tubule
SGLT2 -responsible for 90% of glucose reabsorption
MOA - Blocks glucose reabsorption in the kidney, increases urinary excretion of glucose
◦ Block sodium reabsorption
Results in increased urinary excretion of glucose
SGLT2 Inhibitors
Bexagliflozin, canagliflozin, dapagliflozin,
empagliflozin, ertugliflozin
Bexagliflozin MOA
Blocks glucose reabsorption in the kidney, increases urinary excretion of glucose
◦ Block sodium reabsorption
Results in increased urinary excretion of glucose
canagliflozin moa
Blocks glucose reabsorption in the kidney, increases urinary excretion of glucose
◦ Block sodium reabsorption
Results in increased urinary excretion of glucose
dapagliflozin moa
Blocks glucose reabsorption in the kidney, increases urinary excretion of glucose
◦ Block sodium reabsorption
Results in increased urinary excretion of glucose
empagliflozin moa
Blocks glucose reabsorption in the kidney, increases urinary excretion of glucose
◦ Block sodium reabsorption
Results in increased urinary excretion of glucose
ertugliflozin moa
Blocks glucose reabsorption in the kidney, increases urinary excretion of glucose
◦ Block sodium reabsorption
Results in increased urinary excretion of glucose
SGLT2 Inhibitors (Flozins) ADEs:
◦ Genital?
◦ UT?
◦ Increased urination may lead to?
◦ electrolyte imbalance? which flozin?
◦ bone?
◦ limbs?
◦ metabolic?
◦ pancreas?
◦ Fournier’s gangrene?
◦ Genital mycotic (fungal/yeast) infections
◦ UTIs
◦ Increased urination may lead to volume depletion, hypotension, syncope, falls, and acute kidney injury
◦ Hyperkalemia (canagliflozin)
◦ Fractures (rare)
◦ Increased risk of amputations (rare)
◦ Ketoacidosis (rare)
◦ Acute pancreatitis (rare)
◦ Fournier’s gangrene - infection in the scrotum (which includes the testicles), penis, or perineum (rare
SGLT2 Inhibitors risk of hypo
Hypoglycemia:
Low risk as monotherapy
increased with insulin or secretagogues
SGLT2 Inhibitors benefits
CV
Renal
weight loss
SGLT2 Inhibitors CV
CV benefits
Atherosclerotic Cardiovascular Disease
(ASCVD)
Heart Failure
SGLT2 Inhibitors renal
Renal benefits (Chronic Kidney Disease -
CKD)
SGLT2 Inhibitors weight
weight loss
SGLT2 Inhibitors other info:
renal dosage adjustments
◦ Dosage modification needed with renal impairment
Do not use ertugliflozin with GFR < 60 mL/min
Do not use other SGLT2s with GFR < 45 mL/min
Sulfonylureas (SU)
Glimepiride, glyburide and glipizide
(2 nd generation)
Sulfonylureas (SU) moa
(Secretagogues)
◦ Help the pancreas release more insulin which lowers glucose
◦ Stimulate beta cells causing insulin secretion
Lower fasting and post-prandial glucose
Glimepiride moa
◦ Help the pancreas release more insulin which lowers glucose
◦ Stimulate beta cells causing insulin secretion
Lower fasting and post-prandial glucose
glyburide moa
◦ Help the pancreas release more insulin which lowers glucose
◦ Stimulate beta cells causing insulin secretion
Lower fasting and post-prandial glucose
glipizide moa
◦ Help the pancreas release more insulin which lowers glucose
◦ Stimulate beta cells causing insulin secretion
Lower fasting and post-prandial glucose
Meglitinides
names? similar to? difference?
Nateglinide, repaglinide
Similar to sulfonylureas but shorter acting – taken with meals
◦ hold dose if skipping meals
Meglitinides moa
◦ Increase insulin release in response to food, keeping blood
glucose from rising too high after meals
Lower post-prandial glucose
Nateglinide moa
◦ Increase insulin release in response to food, keeping blood
glucose from rising too high after meals
Lower post-prandial glucose
repaglinide moa
◦ Increase insulin release in response to food, keeping blood
glucose from rising too high after meals
Lower post-prandial glucose
Adverse Drug Effects (ADEs)/Disadvantages of Secretagogues (SU’s and meglitinides)
hypo risk? weight? durability?
HYPOGLYCEMIA!: Caution using with other drugs the cause hypoglycemia
(usually discontinue with use of insulin)
Weight gain
“Durability” declines over time - relatively short-lived efficacy
Thia-zolidine-diones (TZDs)
Pioglitazone and rosiglitazone
TZD moa
◦ Increase glucose uptake into muscles by enhancing the effectiveness of endogenous insulin
◦ bind to nuclear receptor – peroxisome proliferator-activated receptor γ(gamma) - (PPARγ) in adipose, muscle and liver
◦ Reduce glucose output
Pioglitazone moa
◦ Increase glucose uptake into muscles by enhancing the effectiveness of endogenous insulin
◦ bind to nuclear receptor – peroxisome proliferator-activated receptor γ(gamma) - (PPARγ) in adipose, muscle and liver
◦ Reduce glucose output
rosiglitazone moa
◦ Increase glucose uptake into muscles by enhancing the effectiveness of endogenous insulin
◦ bind to nuclear receptor – peroxisome proliferator-activated receptor γ(gamma) - (PPARγ) in adipose, muscle and liver
◦ Reduce glucose output
TZD risk of hypo as monotherapy
Low risk of hypoglycemia when used as monotherapy
TZDs Adverse Effects:
◦ app?
◦CV
◦ Increased risk of?
◦ Edema
◦ Weight Gain
◦ Heart Failure (avoid in patients with symptomatic heart failure)
◦ Increased risk of fractures
TZDs glycemic control over dM course
Glycemic control better sustained over diabetes course
Dipeptidyl-Peptidase-4 Inhibitors (DPP-4 inhibitors,
Alogliptin, Linagliptin, Saxagliptin Sitagliptin
Dipeptidyl-Peptidase-4 Inhibitors moa
◦ Inhibit glucagon release which results in insulin secretion, decreased gastric
emptying and decreased blood glucose level
Linagliptin moa
◦ Inhibit glucagon release which results in insulin secretion, decreased gastric
emptying and decreased blood glucose level
Alogliptin moa
◦ Inhibit glucagon release which results in insulin secretion, decreased gastric
emptying and decreased blood glucose level
saxagliptin moa
dpp4 inhib
◦ Inhibit glucagon release which results in insulin secretion, decreased gastric emptying and decreased blood glucose level
Sitagliptin moa
◦ Inhibit glucagon release which results in insulin secretion, decreased gastric
emptying and decreased blood glucose level
dpp-4 inhib Hypoglycemia with monotherapy
Hypoglycemia with monotherapy – low risk
DPP-4 inhibitors
◦ pancreas?
◦ CV? agents involved?
◦ joints
◦ May be associated with pancreatitis (rare)
◦ New or worsening heart failure (alogliptin and saxagliptin)
◦ May cause severe joint pain (rare
DPP-4 inhibitors additional info :
◦ Dosage modification needed with? agents?
◦ ddi? agents?
◦ Weight?
◦ tolerated?
◦ Dosage modification needed with renal impairment (alogliptin, saxagliptin, sitagliptin)
◦ CYP3A4 drug interaction (linagliptin, saxagliptin)
◦ Weight neutral
◦ Generally well tolerated
Less Commonly Used Medications
Alpha-glucosidase inhibitors
Bile acid sequestrant
Dopaminergic agents
Amylin analog
