Med J Club Dm2 Trt Options.


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Med J Club Dm2 Trt Options.

  1. 2. The case: <ul><li>A 55-y woman with T2DM, obesity,HT, no H/O MAU, retinopathy, or neuropathy. </li></ul><ul><li>She has never had a CV event& no cardiac symptoms. </li></ul><ul><li>She has successfully lost weight (from 5-12 kg) on various diets but each time regained wt, tries to walk 30 min/ day. </li></ul><ul><li>She monitors FG 3/ week, morning FG between 110-140. </li></ul><ul><li>On metformin (2000 mg day) ,glipizide (10 mg twice daily). </li></ul><ul><li>HT treated with HCT 25 mg daily, lisinopril (20 mg daily), aspirin (81 mg daily) simvastatin(20 mg daily). </li></ul><ul><li>She notes that she consistently takes her medications. </li></ul><ul><li>She has a family H/O CVD with early stroke. </li></ul><ul><li>PE: 31,BP 128/78,CVS, abd, neuro exam, is normal. </li></ul><ul><li>Hb1C 8.1%, cr 0.9,no MAU, LFTs normal. </li></ul><ul><li>She seeks advice, </li></ul>
  2. 3. Treatment opotions: <ul><li>Which one of the following treatment options, </li></ul><ul><li>1. Add pioglitazone. </li></ul><ul><li>2. Add NPH insulin before bedtime. </li></ul><ul><li>3. Add exenatide twice daily. </li></ul>
  3. 4. Add Pioglitazone: <ul><li>No data on the optimal trt for failure of dual oral trt. </li></ul><ul><li>PGZ delay the inevitable necessity of initiating insulin&can lead to better response to insulin when needed later. </li></ul><ul><li>TZD lower Hb1C by 2%, few side effects& taken once daily. </li></ul><ul><li>TZD efficacy similar to ins in lowering Hb1C, lower hypoglycemia, similar wt gain, inc in HDL 10-15%, syst BP by 4-5 & carotid thickness& beneficial effect on ischemic events, but more costly. </li></ul><ul><li>RGZ, as initial monotherapy in recent T2DM, maintained targets for longer than did sulfonylurea or metformin, might be due to a beneficial effect on betacell function & addition of pioglitazone to metformin /sulfonylurea expected to have a durable effect on glycemic control maintinance. </li></ul><ul><li>Proinsulin/ insulin, marker of beta-cell function, improved when pioglitazone was added to metformin/sulfonylurea. </li></ul>
  4. 5. Add Pioglitazone: <ul><li>Weight gain 3–4 kg, mitigated by intensifying nutrition </li></ul><ul><li>Reduce bone density, a bone-density scan may be needed in postmenop. </li></ul><ul><li>Rosiglitazone not pioglitazone may increase the risk of ischemic events </li></ul>
  5. 6. Add Pioglitazone: <ul><li>These results support the possibility that pioglitazone may have cardioprotective effects; it would be a good choice for this patient. </li></ul>
  6. 7. Add NPH Insulin before Bedtime: <ul><li>T2DM progressive dis, as declining beta-cell function results in elevations in glycemia year after year unless antidiabetes medications are added or the doses increased. </li></ul><ul><li>Targets: Hb1C 6.5-7% </li></ul><ul><li>Adding a 3rd oral agent as TZD is not recommended; more expensive &not as effective as adding insulin especially at higher initial Hb1c — with less weight gain, no edema, CHF, fractures salutary lipid changes&a lower cost. </li></ul><ul><li>ADA–EASD recommend greater caution in TZD use. </li></ul><ul><li>Adding exenatide in achieve target <6.5% or <7.0%, as expected decrease only 0.5-1.0%, despite the potential weight loss& incur a risk of GITl S/Es & requires twice-daily injs. </li></ul>
  7. 8. Add NPH Insulin before Bedtime <ul><li>Insulin can reduce Hb1c sufficiently ;1.5-3.5% </li></ul><ul><li>Adding an intermediate-acting insulin before bedtime is a relatively straightforward approach </li></ul><ul><li>Some patients may be concerned about self-injection but can be reassured that with modern needles it is a virtually painless process and certainly much less onerous than their finger-stick capillary-glucose measurements. </li></ul><ul><li>Maintaining existing sulfonylurea therapy when supplementing basal insulin requirements means that the required insulin dose is lower </li></ul><ul><li>SE; weight gain 2.8±0.2 kg/hypoglycemic events 5.1%/pat/y. </li></ul><ul><li>Insulin safe starting doses can be easily calculated. </li></ul>
  8. 9. Add Exenatide Twice Daily <ul><li>PGTZ causes fluid retention/weight gain , osteoporosis. </li></ul><ul><li>Insulin effective,but associated with weight gain &needs frequent glucose monitoring to minimize risk of hypos. </li></ul><ul><li>Incretins: (GLP-1) receptor agonists, exenatide&dipeptidyl peptidase IV inhibitors;sitagliptin/vildagliptin11 </li></ul><ul><li>Exenatide (as well as GLP-1)lowers glucose by stimulating insulin secretion/inhibiting glucagon secretion& inhibit gastric emptying,enhance satiety, leading to weight loss. </li></ul><ul><li>Efficacy similar to that of other antidiabetes therapies & exenatide produces more potent control of postprandial glycemia than NPH insulin or pioglitazone, because it suppresses gastric emptying. </li></ul><ul><li>Evidence that it improve betacell function& cardioprotective . </li></ul>
  9. 10. Add Exenatide Twice Daily <ul><li>The actions of GLP-1–receptor agonists on the stimulation of insulin & inhibition of glucagon secretion are glucose-dependent; so very low risk of hypoglycemia in the absence of concomitant sulfonylurea </li></ul><ul><li>It improve the glucose sensitivity of beta cells& potentiate insulin secretion rapidly suggests that discontinuation of the glipizide (or alternatively, the initial reduction of the dose by 50%). </li></ul><ul><li>The addition of exenatide to metformin/ sulfonylurea with an absolute reduction of 0.8 to 1.0%, with 0.9-1.6 kg weight loss </li></ul><ul><li>The use of exenatide&insulin resulted in similar degrees of reduction in glycated hemoglobin & similar hypoglycemic events, but the resultant BW was significantly higher with insulin, 4 kg higher than taking exenatide. </li></ul>
  10. 11. Add Exenatide Twice Daily <ul><li>S/Es: </li></ul><ul><li>GIT; principally nausea 10-20%, abate several weeks after initiation. </li></ul><ul><li>? Pancreatitis </li></ul><ul><li>Expensive&long-term durability/ safety not defined. </li></ul>
  11. 12. Add Exenatide Twice Daily <ul><li>These features make exenatide an appealing option for the treatment of patients in whom existing antidiabetic agents fail to achieve glycemic control. </li></ul>