What are the insulin sensitizers?1) Biguanides...metformin<br>2) TZDs...rozaglidizone and pizaglidizone What is metformin (glucophage) MOA?1) decreases glucose production (gluconeogenesis, glycogenolysis)<br>2) increases insulin sensitivity in liver and skelatal mm What did the&nbsp;UK Prospective Diabetes Study Group (1998) show?1) Metformin&nbsp;reduced all cause mortality and stroke risk in overweight pts with T2DM What is the first line therapy in DM2 algorigthm?1)&nbsp;first line therapy : lifestyle modification AND metformin What is the most common Metformin side effect?1) GI! (diarrhea, N/V, abdominal “bloating”, gas, decreased appetite)<br>2)&nbsp;~10-15% cannot tolerate metformin due to GI side effects<br>3) so put on extended release, and split the dosing up into twice a day What are Metformin side effects?1) GI upset<br>2) lactic acidosis<br>3) B12 deficiency What are the contraindications of Metformin?1) kidney disease...eGFR&lt;30mL/min<br>2) liver disease...hx ETOH abuse<br>3) hx metabolic or lactic acidosis<br>5) hx nfection or heart failure What is metformin dosing?1) start 500mg once in evening<br>2) work up to twice a day<br>2) usual effective dose is 1500-2000mg/day How do we monitor metformin pts?1) A1C every 3-6 months<br>2) creatinine q year<br>3) check CBC/ H/H to screen for anemia What is the MOA of TZDs (glitazones)?1) increase insulin sensitivity via PPAR-gamma&nbsp;<br>2) decr plasma fatty acids Adverse effects of TZDs?1) water retention and edema<br>2) hepatotoxicity...monitor LFTs<br>3) limb fractures<br>4) Pioglitazone (Actos) possibly associated with bladder cancer When do we give TZDs?"1) If you can't tolerate metformin, can't take SFUs, then try this<br>2) but generally we don't give these anymore" What are the insulin secretogogues?"<b><ul><li><div><span style=""font-weight: 400;"">Sulfonylureas</span></div></li><ul><li><div><span style=""font-weight: 400;"">Glyburide (diabeta), Glipizide (glucotrol), Glimepiride (amaryl)</span></div></li></ul><li><div><span style=""font-weight: 400;"">Non sulfonylurea secretagogues</span></div></li><ul><li><div><span style=""font-weight: 400;"">Glitinides, Meglitinides, Glinides (repaglinide and nateglinide)</span></div></li></ul></ul></b>" What is the hypoglycemic risk of insulin secretogogues?"1) highest of any noninsulin tx!!!!!!<br>2) so don't give these to pts also on insulin" What are the SFUs?1)&nbsp;glyburide (Diabeta, Glynase), glipizide (Glucotrol), glimepiride (Amaryl) Pharmokinetics of SFUs?1) hepatic metabolism...CYP450<br>2) once a day dosing Which SFU has less hypoglycemia?glipizide...last 14-16 hours, so if a pt is hypoGlu in ER, give sugar and admit to monitor What are the adverse effects of SFUs?1) hypoglycemia...least of all in glipizide<br>2) weight gain What are contraindications of SFUs?"1) severe liver disease<br>2) renal failure...SFUs have active metabolites that undergo renal clearance...so if kidney's failing, then hypoglycemic" What is the most common non-SFU?Repaglinide&nbsp; (Prandin) What do non-SFUs do?"<b><ul><li><div><span style=""font-weight: 400;"">Mechanism of action similar to </span><span style=""text-decoration-line: underline;"">SFU </span><span style=""font-weight: 400;"">(different receptor)</span></div></li><li><div><span style=""font-weight: 400;"">Require functioning beta cells</span></div></li><li><div><span style=""font-weight: 400;"">rapid onset, short duration...take before meals</span></div></li></ul></b>" What are the adverse effects of Repaglinide (Prandin)?1) hypoglycemia<br>2) weight gain<br>3) LESS SO THAN SFUs Nateglinide (starlix) is the mostly the same as Repaglinide (prandin)...what is different?1) lowest incidence of hypoglycemia of all secretogogues<br>2) active metabolites are excreted...so avoid in renal disease What are uses of meglitinides?"1) commonly, combo with metformin if...pt wants to avoid injections and...can't take SFUs<br>2) sometimes monotherapy if pt can't take metformin or SFUs" "What are the alpha&nbsp;<b><span style=""font-weight: 400;"">glucosidase inhibitors?</span></b>""<b><ul><li><div><span style=""font-weight: 400;"">Acarbose (precose), miglitol (glyset)</span></div></li></ul></b>" What is the MOA of Alpha-Glucosidase Inhibitors do?1) block alpha glucosidase at brush border so...<br>2) less glucose absorption<br>3) miglitol more potent Adverse effects of Alpha-Glucosidase Inhibitors?GI flatulance and diarrhea Downsides of Alpha glucosidase inhibitors?"<b><ul><li><div><span style=""font-weight: 400;"">Not usual first-line therapy</span></div></li><li><div><span style=""font-weight: 400;"">Not useful as monotherapy (not a real reduction in A1C)</span></div></li><li><div><span style=""font-weight: 400;"">Expensive&nbsp;</span></div></li></ul></b>" What is an example of lipase inhibitor?"<b>Orlistat<span style=""font-weight: 400;""> (Xenical, Alli (OTC))</span></b>" What is the MOA of lipase inhibitors? (orlistat)1) increased fecal fat excretion Adverse effects of Orlistat?"<b><ul><li><div><span style=""font-weight: 400;"">GI (cramps, gas, incontinence, oily spotting) in 15-30%</span></div></li><li><div><span style=""font-weight: 400;"">decreased absorption fat soluble vitamins (ADEK)</span></div></li><li><div><span style=""font-weight: 400;"">kidney stones</span></div></li></ul></b>" What is an example of DPP-4 inhibitors?"Gliptans!!!!!<br><b><ul><li><div>Sitagliptin<span style=""font-weight: 400;""> (Januvia)</span></div></li><li><div>Saxagliptin<span style=""font-weight: 400;""> (Onglyza)</span></div></li><li><div><b>Linalgliptin<span style=""font-weight: 400;""> (Tradjenta)</span></b></div></li></ul></b>" What is the MOA of DPP-4 inhibitors? (gliptans)1) prevent breakdown of GLP-1 so...<br>2) increase insulin secretion<br>3) inhibit glucagon "What's the major downside of DPP-4 inhibitors?"1) expensive<br> Benefits of Sitagliptin (Januvia) and Saxagliptin (Onglyza)? (DPP-4 inhibitors)"<b><ul><li><div><span style=""font-style: italic;"">No weight gain</span></div></li><li><div><span style=""font-style: italic;"">Low hypoglycemia risk</span></div></li></ul></b>" Adverse effects of Sitagliptan (januvia) and Saxagliptan (onglyza)?"<ul style=""""><li style=""""><div style="""">Nasopharyngitis</div></li><li style=""""><div style="""">pancreatitis (maybe)</div></li><li style=""""><div style="""">headache</div></li></ul>" Other DPP-4 inhibitor?"<b><div><br></div><ul><li><div>Linagliptin <span style=""font-weight: 400;"">(Tradgenta)</span></div></li><ul><li><div><span style=""font-weight: 400;"">Biliary tract secretion (unique to DPP-4 inhibitors)</span></div></li><li><div><span style=""font-weight: 400;"">easier on kidneys...no renal dosage necessary</span></div></li></ul></ul></b>" What is the MOA of SGLT-2s? (flozans)1) prevent glucose reabsorption at PCT so...<br>2) pee out glucose<br>3) H2O follows water, so helpful in CHF pts Benefits of SGLT-2 inhibitors? (flozans)No hypoglycemia What are the SGLT-2 inhibitors?Flozans...<br>1)&nbsp;Canagliflozin (Invokana)<br>2) Dapagliflozin (Farxiga)<br>3) Empagliflozin (Jardiance) Usage of Canagliflozin (Invokana)?1) combo therapy with metformin in diabetic CHF pts Benefits of Canagliflozin (Invokana)?"<b><ul><li><div>weight<span style=""font-weight: 400;""> </span><span style=""text-decoration-line: underline;"">loss</span></div></li><li><div>Low incidence hypoglycemia</div></li><li><div><b><span style=""text-decoration-line: underline;"">Decrease </span><span style=""font-weight: 400;"">in BP (in those with hypertension) due to osmotic diuresis</span></b></div></li></ul></b>" Adverse reactions of SGLT-2s?"<div><i><br></i></div><ul style=""""><li style=""""><div style="""">UTI</div></li><li style=""""><div style="""">Vulvovaginal candida</div></li><li style=""font-weight: bold;""><div><span style=""font-weight: 400;"">Hypotension, dehydration</span></div></li><ul style=""font-weight: bold;""><li><div><span style=""font-weight: 400;"">Especially if taking ACE inhibitors, ARBs&nbsp;</span></div></li></ul><li style=""font-weight: bold;""><div><span style=""font-weight: 400;"">Kidney injury</span></div></li><li style=""font-weight: bold;""><div><span style=""font-weight: 400;"">bone fractures...due to demineralization</span></div></li><li style=""font-weight: bold;""><div><span style=""font-weight: 400;"">Euglycemic diabetic ketoacidosis(rare for T2DM!!!)</span></div></li></ul>" Contraindications for SGLT-2s?1) renal insufficiency What is an example of a bile acid sequestrants?&nbsp;Colesevelam Adverse effects of Bile acid sequestrins?"<ul style=""""><li style=""font-weight: bold;""><div><span style=""font-weight: 400;"">GI&nbsp;</span></div></li><li style=""font-weight: bold;""><div><span style=""font-weight: 400;"">May increase TG</span></div></li><li style=""font-weight: bold;""><div><span style=""font-weight: 400;"">Possible malabsorption of fat soluble vitamins </span><span style=""font-weight: 400; font-style: italic;"">ADEK</span></div></li><li style=""font-weight: bold;""><div><span style=""font-weight: 400;"">Drug-drug interactions due to decreased absorption</span></div></li><ul style=""font-weight: bold;""><li><div><span style=""font-weight: 400;"">Levothyroxine, glyburide, OC, phenytoin, warfarin, digoxin</span></div></li></ul><li style="""">***not typically recommended by up to date</li></ul>" What are benefits of metformin (glucophage)?"<b><ol><li><div><span style=""font-weight: 400;"">Low risk hypoglycemia (“euglycemic”)</span></div></li><li><div><span style=""font-weight: 400;"">Reduction of triglycerides and LDL</span></div></li><li><div><span style=""font-weight: 400;"">Modest weight loss</span></div></li><li><div><span style=""font-weight: 400;"">Short half-life</span></div></li></ol></b>" What are the kinetic of metformin (glucophage)?"<b><ol><li><div><span style=""font-weight: 400;"">Not metabolized</span></div></li><li><div><span style=""font-weight: 400;"">Renally excreted</span></div></li></ol></b>" What are the TZDs (glitazones)?1) rosiglitzaone (Avandia)<br>2) Pioglitazone (Actos) What are the benefits of TZDs (glitazones)?Low hypoglycemic risk when given on its own What are contraindications of TZDs (glitazones)?1) heart failure<br>2) pregnancy<br>3) osteoporosis Mechanism of action of SFUs?"<b><ol><li><div><span style=""font-weight: 400;"">Enhance insulin secretion in non-glucose dependant manner</span></div></li><li><div><span style=""font-weight: 400;"">Needs functioning beta cells</span></div></li></ol></b>" What are the non-SFUs?"<b><span style=""font-weight: 400;"">1) Glitinides<br>2) meglitinides<br>3) glinides</span></b>" What are the glinides?1) repaglinide (prandin)<br>2) nateglinide (starlix) What are the kinetics of Repaglinide (prandin)?1) CYP450<br>2) RENAL DOSING NOT NECESSARY What are contraindications of Repaglinide (prandin)?liver disease Contraindications for alpha glucosidase inhibitors?1) intestinal disorder<br>2) not recommended in liver/kidney disease What are the uses of Lipase inhibitors?1) NOT DIABETIC MONOTHERAPY<br>2) use in obese diabetic pts to lower weight<br>3) currently impossible to get hands on bc used solely as weight loss drug Kinetics of Sitagliptin (Januvia) and Saxagliptin (Onglyza)?1) renal dosage necessary Which SGLT-2 inhibitor has the best CV outcomes? (flozans)Empagliflozin (Jardiance) What is the MOA of Bile acid sequestrants? (colesevelam)"<b><ol><li><div><span style=""font-weight: 400;"">Unknown</span></div></li><li><div><span style=""font-weight: 400;"">Decrease glucose absorption</span></div></li><li><div><span style=""font-weight: 400;"">Lower LDL</span></div></li></ol></b>"