Download Diabetes Therapy and Problems for the Cardiologist. Quali

Diabetes Therapy and Problems
for the Cardiologist.
Quali difficolta pone la terapia
diabetologica al cardiologo
Mariell Jessup MD, FAHA, FACC, FESC
Professor of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Disclosure: I have no conflicts with respect to this lecture
ADA/EASD 2012 position statement
The American Diabetes Association (ADA) and
the European Association of the Study of Diabetes (EASD)
Metformin
mechanism of action
*effective only in the presence of insulin
*major effect is to decrease hepatic glucose output,
increases insulin-mediated glucose utilization in
peripheral tissues (such as muscle and liver)
*an anti-lipolytic effect that lowers serum free fatty
acid concentrations, reducing substrate availability
for gluconeogenesis
Metformin
advantages
• Promotes weight loss or
stabilization of weight
• Lipid lowering activity, decreased
triglycerides and free fatty acids
• Less likely to cause hypoglycemia
• Works well in combination
Metformin
adverse effects
• Gastrointestinal: metallic taste in the mouth, mild
anorexia, nausea, abdominal discomfort, and soft
bowel movements or diarrhea
• Reduces intestinal absorption of vitamin B12 in
up to 30% of patients, and lowers serum vitamin
B12 concentrations in 5 to 10%
• Lactic acidosis: most important in renal failure,
but heart failure and shock are always cited.
– GFR < 60mL/min
– Iodinated contrast
ADA/EASD 2012 position statement
The American Diabetes Association (ADA) and
the European Association of the Study of Diabetes (EASD)
Sulfonylureas
mechanism of action
• increased responsiveness of beta cells to both
glucose and non-glucose secretagogues (such as
amino acids), resulting in more insulin being
released at all blood glucose concentrations.
• useful only in patients with some beta cell
function.
• Drugs in this class: Glipizide, glyburide
(glibenclamide), gliclazide, and glimepiride
Sulfonylureas
adverse effects: hypoglycemia
■After exercise or a missed meal
■When the drug dose is too high
■With the use of longer-acting drugs (glyburide,
chlorpropamide)
■In patients who are undernourished or abuse alcohol
■In patients with impaired renal or cardiac function or
gastrointestinal disease
■With concurrent therapy with salicylates, sulfonamides,
fibric acid derivatives (such as gemfibrozil), and warfarin
■After being in the hospital
Increased risk after MI????
ADA/EASD 2012 position statement
The American Diabetes Association (ADA) and
the European Association of the Study of Diabetes (EASD)
Thiazolidinediones
mechanism of action
• bind to and activate peroxisome proliferatoractivated receptors (PPARs), which regulate gene
expression in response to ligand binding
• increase insulin sensitivity by acting on adipose,
muscle, and liver to increase glucose utilization
and decrease glucose production
• drugs in this class: troglitazone, pioglitazone,
and rosiglitazone.
Thiazolidinediones
effects and adverse events
• Beneficial effects on :dyslipidemia, markers of
inflammation, vascular smooth muscle
proliferation, vascular reactivity, endothelial
function, carotid intima media thickness, and
progression of atherosclerosis on coronary
intravascular ultrasound.
• But…weight gain, fluid retention, heart failure,
myocardial infarction, and fractures occur
• RECORD trial (3.75 years follow-up) increased risk of
HF (HR 2.24)in rosiglitazone combinations compared
with metformin plus sulfonylurea.
DPP-4 inhibitors
mechanism of action
• Drugs in this class: sitagliptin, saxagliptin,
linagliptin, alogliptin, vildagliptin
• Dipeptidyl peptidase 4 (DPP-4) is a ubiquitous
enzyme expressed on the surface of most cell
types that deactivates a variety of other bioactive
peptides, including GIP and GLP-1; therefore,
its inhibition could potentially affect glucose
regulation through multiple effects
DPP-4 inhibitors
adverse events
• well tolerated in short-term studies.
• no effects on body weight or risk of
hypoglycemia (in the absence of concomitant
treatment with insulin or sulfonylureas
• common side effects include: headache,
nasopharyngitis, and upper respiratory tract
infection
• long-term safety with DPP-4 inhibitors has not
been established.
GLP-1 receptor agonists
mechanism of actions
• GLP-1-based therapies affect glucose control
through several mechanisms: enhancement of
glucose-dependent insulin secretion, slowed
gastric emptying, regulation of postprandial
glucagon, and reduction of food intake
• Drugs in this class: xenatide, liraglutide,
albiglutide, taspoglutide, lixisenatide
GLP-1 receptor agonists
effects and adverse events
• potential benefit: weight loss
• most common adverse events:
– nausea, vomiting, and diarrhea
– pancreatitis is serious
Diabetes Therapy
and Problems for the Cardiologist.
• Since so many of our patients have diabetes, we
must learn these new drugs
• Huge controversy over the long-term
cardiovascular effects of diabetic drugs
• Edema is common with TZDs; lactic acidosis
with metformin is probably not common
• The GLP-1 agonists are potentially useful in HF.