Control of Blood Glucose and Drug Treatment of Diabetes Flashcards

1
Q

TYPE OF INSULIN:
USE:
RAPID ACTING
Humalog, Amelog* (insulin lispro)

A

Bolus dosing(meals) and insulin
pumps (administration ranges 5-15
minutes before meals –see specific
product information

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2
Q

TYPE OF INSULIN:
USE:
SHORT ACTING
Humulin R or Novolin R - Regular
insulin -

A

Bolus dosing(meals)
(administration ranges 15-30
minutes before meals –see specific
product information

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3
Q

TYPE OF INSULIN:
USE:
INTERMEDIATE-ACTING
Humulin N or Novolin N - NPH ~

A

Basal-like (administration Q day
to BID)

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4
Q

TYPE OF INSULIN:
USE:
ONG ACTING
Lantus, Basaglar* (insulin
glargine) – 100 units/mL
Toujeo (insulin glargine) – 300
unitls/mL
Levemir (insulin detemir) – dc
2024

A

Basal (administration Q day)

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5
Q

TYPE OF INSULIN:
USE:
ULTRA LONG ACTING
Tresiba (insulin degludec)

A

Basal (administration Q day,
anytime of day

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6
Q

— Glucose homeostasis:

A

balance between hepatic glucose
production and peripheral glucose uptake and utilization

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7
Q

— Glucose –

A

source of energy

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8
Q

— Insulin -

A

most important regulator of glucose/metabolic
equilibrium

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9
Q

— Pancreatic Islet Hormones (endocrine)
◦ Maintains — balance
◦ 4 types of peptide-secreting cells:

A

glucose

– Beta (B) – secrete insulin
– Alpha (A) – secrete glucagon
– Delta (D) – secrete somatostatin
– PP (also known as gamma) – secrete pancreatic polypeptide

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10
Q

Relationship between Glucose and Insulin

A

— Glucose is the main factor
controlling synthesis and
secretion of insulin

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11
Q

Two ways insulin is released:

A

◦ Steady basal release of insulin
◦ Response to increased glucose

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12
Q

About — of insulin stored in
the pancreas of an adult is
secreted daily

A

1/5

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13
Q

Glucose stimulated insulin secretion

A

— 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

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14
Q

Diabetes Mellitus (DM)
— A group of complex chronic metabolic disorders
characterized by high blood glucose concentrations
(hyperglycemia)
(3)

A

◦ Insulin deficiency
◦ Often combined with insulin resistance
◦ Abnormalities in the metabolism of carbohydrates, proteins, fats
and insulin

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15
Q

Hyperglycemia due to:
(3)

A

◦ Uncontrolled hepatic glucose output
◦ Reduced uptake of glucose by skeletal muscle
◦ Reduced glycogen synthesis

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16
Q

Types of DM – Two Major Types
— Type 1 (T1DM)
(3)

A

◦ 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

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17
Q

ypes of DM – Two Major Types
— Type 2 (T2DM)

A

◦ 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

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18
Q
A
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19
Q

— Other forms

A

(e.g. gestational diabetes, medications - glucocorticoids)

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20
Q

CLINICAL PRESENTATION
* Symptoms may include (5)

A

polydipsia,
polyphagia, polyuria, nocturia, blurred
vision. (More common on type 1/
occurs in varying degree in Type 2
DM).

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21
Q
  • Type 1 DM often associated with
    (2)
A

weight loss, ketoacidosis (dehydration)

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22
Q
  • Majority of Type 2 patients are
    — and diagnosed by
    laboratory testing
A

asymptomatic

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23
Q

Screening for T2DM and Prediabetes in Asymptomatic
Patients

A

— 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.

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24
Q

ADA’s Diabetes
Risk Test
Increasing aging
population and
numbers of

adolescents,
teenagers and
adults = rapid
increases in
prevalence

A

overweight

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25
A1C =
Hemoglobin A1c. Glucose binds hemoglobin. The A1C is a simple lab test that shows the average amount of glucose in a person’s blood over the last 3-4 months.
26
Complications — Macrovascular (3) — Microvascular (4) — Strategic Risk Reduction Strategies
◦ Brain ◦ Heart ◦ Extremities (peripheral vascular disease) ◦ Eyes ◦ Kidney ◦ Nerves – Peripheral – Autonomic ◦ Periodontal disease
27
Glycemic Goals
28
Additional DM Goals – Risk Reduction Strategies — Reduce the risk of (2)(and other) complications through glycemic control and controlling co-morbid conditions to which DM contributes
macrovascular and microvascular
29
Reduce cardiovascular risk factors (3)
– Control BP – Control lipids – Smoking Cessations
30
◦ Reduce the risk of vaccine-preventable diseases (1)
– Immunizations – Examples: Flu, Tdap/Td, Pneumococcal, Hepatitis B (others)
31
— Minimize periodontal complications due to diabetes mellitus, provide
safe and effective dental care and promote good oral health
32
Non-pharmacologic therapy for DM — Medical Nutrition Therapy (4)
◦ 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
33
— Physical Activity (5)
◦ 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
34
Insulin — History of insulin in the treatment of diabetes = interesting ◦ Insulin destroyed in --- ◦ Before insulin therapy Type I DM = ◦ Breakthrough in 1920’s when insulin was isolated – Noble Prize = Banting and Best (University of Toronto) ◦ (2) sources – Bovine - discontinued in US in1978 – Porcine manufactured in US until 2005 ◦ Significant variability between batches ◦ Allergies – ---
GI tract death sentence (wasting and dying from ketoacidosis) Porcine or Bovine immune response to animal-based products
35
Current Insulin therapy
— 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
36
Rapid-acting Insulin — (3)
Rx only — Appearance- clear/colorless — rDNA – human insulin analogs
37
Short-acting (Regular) Insulin (3)
— Non-Rx – 100 units/ml (Humulin R U-500 - RX) — Appearance- clear/colorless — rDNA – human insulin analogs
38
Inhaled Insulin - Afrezza (8)
— 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!
39
Intermediate-acting (NPH)Insulin (4)
— NPH - Neutral Protamine Hagedorn — Non-Rx — Appearance - cloudy — rDNA – human isophane insulin suspension
40
Long-acting Insulin —(4)
Rx only — Appearance – clear, colorless — rDNA – human insulin analogs
41
Ultra Long-acting Insulin (3)
— Rx only — Appearance – clear, colorless — rDNA – human insulin analogs
42
— NPH/Regular
◦ 70%/30% ◦ 50%/50%
43
— Insulin aspart protamine suspension/ insulin aspart solution
— 70%/30%
44
— Insulin degludec and insulin aspart injection
— Ryzodeg 70/30 ®
45
— Insulin lispro protamine/insulin lispro
◦ 75%/25%
46
— Insulin lispro protamine/insulin lispro
◦ 50%/50%
47
— 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
48
* Reusable insulin pen– * Disposable insulin pens -
must load with insulin cartridges - sold separately come filled with insulin and are thrown away when empty
49
Examples of Pens used in DM
— Apidra® SoloStar®, Humalog® KwikPen™, Humulin® Pen, Lantus® Solostar®, Levemir® FlexPen®, NovoLog® Mix FlexPen®, NovoPen Junior®, AutoPen®
50
Common Insulin Regimens (2)
— Basal-bolus regimen (4 injections total/day) ◦ Mimic physiologic insulin release
51
Rapid-acting/NPH (2)
— 2 injections/day ◦ Rapid or regular insulin mix with NPH
52
Continuous Insulin Infusion Pumps
— 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 — Programed external pump - worn continuously ◦ Delivers insulin through a cannula inserted just beneath the surface of the skin ◦ One injection site for 72 hrs — Many pumps have Continuous Glucose Monitoring (CGM) system integrated within the pump or they can be used separately
53
Continuous Insulin Infusion Pumps — Advantages (3)
◦ Improved glycemic control ◦ Decreased A1c ◦ Decreased risk of hypoglycemia
54
Continuous Insulin Infusion Pumps ¾ Adverse Effects:
* 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 ¾ Dental: Either Hypo- or Hyperglycemia may occur! * If pt confused/unresponsive, always push “suspend” button immediately. * Then check display to assess last glucose trend.
55
Glucose Monitors and Continuous Glucose Monitoring (CGM) — Purpose:
to monitor blood glucose levels in patients with diabetes — Safety and efficacy of insulin and other diabetic drugs
56
— Blood Glucose Meters (many brands)
◦ 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.
57
— 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
58
Use of insulin in DM — Type 1 (3)
◦ 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
59
Use of insulin in DM — Type 2 (5)
◦ 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
60
Insulin Dosing — Type 1 (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
61
Insulin dosing — Type 2 (4)
◦ 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
62
Adverse Effects of Insulin — HYPOGLYCEMIA! (7)
◦ Highest risk of any diabetes medication ◦ Tighter control (of glucose) = é risk of hypoglycemia ◦ 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 ◦ Manage patient as if hypoglycemic, until proven otherwise ◦ Check blood glucose with monitor ◦ 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.
63
Definitions for Hypoglycemia ◦ Serious, clinically significant: < -- mg/dL ◦ Glucose Alert Value: < -- mg/dL
◦ Not all patients will experience hypoglycemia – Certain antidiabetic drugs and patient risk factors increase risk 54 70
64
Management of Hypoglycemia — Rule of 15s — Treat if < -- mg/dl
70 * 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
65
Management of Hypoglycemia — Unconscious patient or unable to swallow (6)
◦ 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. ◦ 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
66
Therapy for Type 2 DM (6)
— Diet Management — Oral antidiabetic agents ◦ Possess varying amounts of hypoglycemic risk — Insulin therapy — Other injectable therapy (GLP1 inhibitors) — Be able to identify the magnitude of risk for hypoglycemic for various antidiabetic agents — Many classes and lots endings and abbreviations for drug classes to keep up with
67
Biguanides — Metformin (Glucophage) only available drug in class — MOA (4)
◦ Keeps the liver from releasing too much glucose ◦ ̄ Hepatic glucose production (gluconeogenesis – markedly increased in Type 2) – PRIMARY MECHANISM ◦ Decreases insulin resistance (increases insulin sensitivity)- glucose utilization in muscle and adipose tissues ◦ Inhibits intestinal absorption of glucose
68
Metformin
— 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 neutral/ameliorates insulin-associated weight gain — Low risk of hypoglycemia with monotherapy — 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 — Risk of B12 deficiency (should be checked annually) — 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)
69
Glucagon Like Peptide-1 Receptor Agonists (GLP 1-RA, “incretin mimetics” - Glutides) emptying
— Albiglutide, Dulaglutide, Exenatide, Liraglutide, Lixisenatide, Semaglutide — Most options available as injections (sc) only — Semaglutide available sc and po — Dosing frequency varies – BID, daily and weekly depending on medication and formulation — 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
70
GLP 1- Receptor Agonists
— Benefits ◦ Weight loss ◦ Higher dosages approved for weight loss – semaglutide (Wegovy) - injection – liraglutide (Saxenda) - injection ◦ CV benefits (except lixisenatide and immediate-release exenatide) – Atherosclerotic Cardiovascular Disease (ASCVD) ◦ Kidney benefits – Chronic Kidney Disease (CKD) (liraglutide, semaglutide) – but SGLT2 preferred — ADEs – nausea, diarrhea, injection site reactions, pancreatitis (rare), gallbladder disease, risk of Thyroid-C cell tumors — Hypoglycemia: low risk with monotherapy (may increase risk in combination therapy with sulfonylureas/others that cause hypoglycemia)
71
Glucose-dependent insulinotropic polypeptide (GIP) agonist + Glucagon-like, peptide-1 (GLP-1) agonist (“twincretin”) — Tirzepatide (Mounjaro) – FDA approved 2022 for the treatment of adults with type 2 diabetes ◦ Weight management indication ◦ MOA:
increases insulin secretion in response to elevated glucose, decreases glucagon secretion, slows gastric emptying
72
GIP/GLP-1 Receptor Co-agonist (“twincretin”) — ADEs: (5) — Additional Information: (5)
◦ 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 ◦ 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
73
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
74
SGLT2 Inhibitors (Flozins) — Bexagliflozin, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin — ADEs
◦ 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) ◦ Hypoglycemia: – Low risk as monotherapy – with insulin or secretagogueus
75
SGLT2 Inhibitors (Flozins) — Benefits (3) — Other information (3)
◦ CV benefits – Atherosclerotic Cardiovascular Disease (ASCVD) – Heart Failure ◦ Renal benefits (Chronic Kidney Disease - CKD) ◦ Weight loss (less than GLP1 agonists) ◦ 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
76
Sulfonylureas (SU)
— Glimepiride, glyburide and glipizide (2 nd generation) — MOA (Secretagogues) ◦ Help the pancreas release more insulin which lowers glucose ◦ Stimulate beta cells causing insulin secretion — Lower fasting and post-prandial glucose
77
Meglitinides
— Nateglinide, repaglinide — Similar to sulfonylureas but shorter acting – taken with meals ◦ hold dose if skipping meals — MOA (Secretagogues) ◦ Increase insulin release in response to food, keeping blood glucose from rising too high after meals — Lower post-prandial glucose
78
Adverse Drug Effects (ADEs)/Disadvantages of Secretagogues — Insulin secretors/secretagogues (SU’s and meglitinides) (4)
— 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
79
Thia-zolidine-diones (glitazones, TZDs)
— Pioglitazone and 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 — Low risk of hypoglycemia when used as monotherapy
80
TZDs Adverse Effects and Additional Information — ADEs (4) — Additional information (1)
◦ Edema ◦ Weight Gain ◦ Heart Failure (avoid in patients with symptomatic heart failure) ◦ Increased risk of fractures ◦ Glycemic control better sustained over diabetes course
81
Dipeptidyl-Peptidase-4 Inhibitors (DPP-4 inhibitors, “gliptins”)
— Alogliptin, Linagliptin, Saxagliptin Sitagliptin — MOA ◦ Inhibit glucagon release which results in insulin secretion, decreased gastric emptying and decreased blood glucose levels — Hypoglycemia with monotherapy – low risk
82
DPP-4 inhibitors Adverse Effects and Additional Information — ADEs (3) — Additional information (4)
◦ May be associated with pancreatitis (rare) ◦ New or worsening heart failure (alogliptin and saxagliptin) ◦ May cause severe joint pain (rare) ◦ Dosage modification needed with renal impairment (alogliptin, saxagliptin, sitagliptin) ◦ CYP3A4 drug interaction (linagliptin, saxagliptin) ◦ Weight neutral ◦ Generally well tolerated
83
Less Commonly Used Medications (4)
— Alpha-glucosidase inhibitors — Bile acid sequestrant — Dopaminergic agents — Amylin analog
84
Take Home Points:
— Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by high blood glucose concentrations ◦ Insulin deficiency ◦ Often combined with insulin resistance ◦ Risks for microvascular and macrovascular complications ◦ Uncontrolled diabetes leads to devastating consequences — T1DM = insulin therapy + diet management — T2DM = diet management with oral and/or insulin/GLP1RA therapy — The mechanisms of action of the drug therapy involved with treating DM involves either providing/increase insulin and/or lowering glucose by various means — Hypoglycemia is the most dangerous adverse event of some diabetic medications ◦ Knowing which ones and how to manage is important for dental practice