Antidiabetic Drugs
Antidiabetic Drugs
Antidiabetic Drugs
Darweesh O. Chua
Cheley Marie Co
Diabetes Mellitus
Diabetes Mellitus
● Group of common metabolic disorders that share the phenotype of
hyperglycemia
● Factors contributing to hyperglycemia:
○ reduced insulin secretion, decreased
○ glucose utilization
○ increased glucose production
Epidemiology
● 1 in 14 Filipino adults lives with diabetes
● 2019, IDF
● 3,993,300 out of 63,265,700 filipino adult have diabetes
● 6.3 prevalence of diabetes in adults
● IDF projection: by 2030, number of adults with diabetes in PH will further
rise to 5,289,700 and aby 2045 7,267,400
Diagnosis
Screening
● Fasting plasma glucose or HbA1c
○ a large number of individuals who meet the current criteria for DM are
asymptomatic and unaware that they have the disorder
○ epidemiologic studies suggest that type 2 DM may be present for up to
a decade before diagnosis some
○ individuals with type 2 DM have one or more diabetes-specific
complications at the time of their diagnosis
○ treatment of type 2 DM may favorably alter the natural history of DM
○ diagnosis of prediabetes should spur efforts for diabetes prevention
Screening
ADA criteria for the Dx of diabetes
1. A1C ≥6.5%
OR
2. FPG ≥126 mg/dL (7 mmol/L)
OR
3. 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an
OGTT
OR
4. In a patient with classic symptoms of hyperglycemia or
hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1
mmol/L).
Regulation of Glucose Homeostasis
Insulin Secretion
Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus
Immune-mediated destruction of Insulin resistance and abnormal
the pancreatic beta cells and insulin secretion
insulin deficiency
Can develop at any age
Pathophysiology - islet cell autoantibodies (ICAs) - impaired insulin secretion
- activated lymphocytes in the - insulin resistance
islets, and peripancreatic lymph - excessive hepatic glucose
nodes production
- T lymphocytes that proliferate - abnormal fat metabolism
when stimulated with islet - systemic low-grade inflammation
proteins
- release of cytokines within the
insulitis
Diabetes Mellitus:
Management and
Therapies
Overall Goals
● Eliminate symptoms related to hyperglycemia
● Reduce or eliminate the long-term microvascular and macrovascular
complications of DM
● Allow the patient to achieve as normal a lifestyle as possible
Lifestyle Management
Diabetes Self-Management Education and Support (DSMES)
● refers to ways to improve the patient’s knowledge, skills, and abilities
necessary for diabetes self-care and should also emphasize psychosocial
issues and emotional well-being
Nutrition Therapy
● high-quality, nutrient-dense with limits on carbohydrate intake required for
glycemic control and weight management
Lifestyle Management
Physical Activity
● ADA recommends 150 min/week (distributed over at least 3 days) of
moderate aerobic physical activity with no gaps longer than 2 days.
Psychosocial Care
● Depression, anxiety, or “diabetes distress,” defined by the ADA as “…
negative psychological reactions related to emotional burdens…in having to
manage a chronic disease like diabetes,” should be recognized and may
require the care of a mental health specialist
Management of
T1DM
Insulin Regimens
● Short-acting insulin analogues - injected just before (<10 min)
● Regular insulin - 30–45 min prior to a meal.
Biguanides,
thiazolidinedines
BIGUANIDES
BIGUANIDES
Metformin
METABOLISM AND EXCRETION:
● T ½ = 1.5-3 hrs
● Renally excreted
● eGFR
○ 60 - 45 mL/min per 1.73 m2 = SAFE
○ 45 - 30 mL/min per = USE CAUTIOUSLY
○ < 30 mL/min/1.73 m = CONTRAINDICATED!
Metformin
CLINICAL USE
● Insulin-sparing agent
● DOES NOT increase body weight
● DOES NOT provoke hypoglycemia
● Max dose: 2.55g/day
● w/
Metformin
Toxicities:
● Gastrointestinal
○ Anorexia, N/V, abdominal discomfort, diarrhea
● Vitamin B12 deficiency (prv: inc Ca intake)
● Lactic acidosis
○ Inc in conditions of tissue hypoxia, renal failure,
inc prod. Of LA
Sulfonylureas, Non-sulfonylureas
(Meglitinides, D-phenylalanine derivatives)
INSULIN
SECRETAGOGUES
SULFONYLUREAS
1ST GENERATION 2ND GENERATION
Toxicities:
● Hypoglycemia
● Skin rashes or
hematologic toxicity
● Weight gain
Non-sulfonylureas
➔ Meglitinides
◆ Repaglinide
● S/E: hypoglycemia, secondary failure
➔ D-phenylalanine derivative
◆ Nateglinide
● promotes a more rapid but less-sustained secretion of
insulin than other available oral antidiabetic agents
● Fewer episodes of hypoglycemia.
DRUGS THAT AFFECT ABSORPTION OF
GLUCOSE
α-glucosidase inhibitors
-gliflozin
(SGLT2) INHIBITORS
● Canagliflozin, dapagliflozin, and empagliflozin
● Used in combination with metformin or a sulfonylurea for
treatment of type 2 diabetes
● A/E: headache, nasopharyngitis, and URTIs
● CI: eGFR <45 mL/min/1.73 m2
Pramlintide, colesevelam,
bromocriptine
OTHER HYPOGLYCEMIC
DRUGS
● Pramlintide - injectable synthetic analog of amylin
○ suppresses glucagon release, slows gastric emptying, and works in
the CNS to reduce appetite
○ A/E: hypoglycemia and gastrointestinal disturbances
● Colesevelam
○ A/E: gastrointestinal complaints
● Bromocriptine - dopamine agonist
INSULIN THERAPY
GENERAL
IN T2DM
PRINCIPLES
Generally provided in three ways:
❖ Insulin is secreted in a
pulsatile manner
❖ Intensive insulin therapy
➢ basal insulin + short-
acting or rapid-acting
insulins ≥ 3 times daily
before meals
DISADVANTAGES
❖ Weight gain
❖ Hypoglycemia
Monitoring Glycemia
❖ Glycated hemoglobin (A1C)
➢ ≤ 7.0 percent
❖ Blood glucose monitoring
➢ FBS of 80 to 130 mg/dL AND postprandial
glucose (90-120 minutes after a meal) < 180
mg/dL
➢ higher fasting glucose target - older patients, w/
CKD, or those with other risk factors for
hypoglycemia
WHEN TO INITIATE INSULIN?
❖ Severe hyperglycemia on presentation
➢ Symptomatic or severe hyperglycemia with ketonuria
➢ RBS consistently >300 mg/dL but without ketonuria or
spontaneous weight loss, in whom type 1 diabetes is not likely
❖ Difficulty distinguishing type of diabetes
❖ Pancreatic insufficiency
❖ Persistent hyperglycemia on oral agents
WHEN TO START?