Unmasking the evidence of efficacy and safety. Cheaper or Better DEBATE (pros) Panagiotis Halvatsiotis 2 nd Department of Internal Medicine Research Unit & Diabetes Center of Athens University Medical School University General Hospital«Attikon»
Disclosures No Conflict of Interest
Diabetes Mellitus in USA
DM in USA Financial Burden Diabetes Care 2014; 37:3172 3179
"Ambulatory Treatment of Type 2 Diabetes Mellitus 1997-2012" ambulatory diabetes visits increased from 23 million in 1997 to 35 million in 2007. However, fell slightly to 31 million in 2012 biguanide increased from 24 % in 1997 to 53 % of treatment visits in 2012. continuous decline in SU use from 61% in 1997 to 22 % in 2012. Diabetes Care, Nov 2013
"Ambulatory Treatment of Type 2 Diabetes Mellitus 1997-2012" glitazone medications increased from 6% of treatment visits in 1997 to 41% in 2005, but declined to 16% in 2012. The amount of money spent on medications increased 61% 2008 & 2012, which was driven mostly by the use of insulin glargine & DPP-4 inhibitors. Diabetes Care, Nov 2013
Projected prevalence of cancers, diabetes, coronary heart disease stroke, per 100 000 of the population by 2030 by country. doi: 10.1136/bmjopen-2014-004787 BMJ Open 2014 4: Laura Webber, Diana Divajeva, Tim Marsh, et al. interventions: a modelling study countries and the impact of effective diseases in the 53 WHO Europe
GENERICS EXIST FOR Sulfonylureas Metformin Glitazones α-glucosidase inhibitors Meglitinides Old fashioned insulins
NEW ORAL AGENTS in DM2 DPP-4 inhibitors SGLT-2 inhibitors
DPP-4 inhibitors DM2 Insulin Glucose Reduced incretin effect Reduced islet function hyperglycemia Glucagon DPP-4 inhibition Insulin Glucose Increased indogenous incretin effect Increased islet function Glucagon Improved glycemia DPP-4=dipeptidyl peptidase-4; T2DM=type 2 diabetes mellitus Adapted from Unger RH. Metabolism. 1974; 23: 581 593; Ahrén B. Curr Enzyme Inhib. 2005; 1: 65 73.
SGLT-2 inhibitors
Can you cure my diabetes doc! YES, we have now government approved guidelines (Roy Taylor, Newcastle UK)
Beyond Compliance Is Adherence Does the patient follows prescription? Source: National Association of Chain Drug Stores, Pharmacies: Improving Health, Reducing Costs, July 2010. Based on IMS Health data]
Beyond Compliance Is Adherence Reasons to deviate?
Non Adherence Consequencies in DM2 Gibson et al, Am J Manag Care 2010, 16(7):589-600
Non Adherence Cost Less compliance fortifies financial burden for the health provider?
REASONS FOR NON ADHERENCE CONCERNS FOR IN DM2 1. Hypoglycemia 2. BW increase 3. Cardiovascular Risk Hauber et al, Diabet Med 26:416-424, 2009
Emergeny hospitalisations for Adverse Drug Reactions 2007 2009 Amongst population > 64 years Annual estimated ER visits 265.802 Emergency hospitalization 99.628 Budnitz et al. N Engl J Med 2011; 365:21.
Emergency Hospitalizations for Adverse Drug Effects in Older Americans
National Trends in US Hospital Admissions for Hyperglycemia and Hypoglycemia Among Medicare Beneficiaries, 1999 to 2011. Hospital admission rates for hypoglycemia now exceed those for hyperglycemia JAMA Intern Med. 2014 May 17. doi: 10.1001/jamainternmed.2014.1824
Hypoglycemia Admissions University General Hospital «Attikon» 2007-2012 Diabetics>65 yo 158 (325) 49,1% Neurological Symptoms 23,6% Infection 3,6% Stroke 3,6% CVD 3,6% Kidney Failure 5,5% Neoplasms COPD- Liver Failure. 4 Deaths
Mortality at 1 st month (%) Glycemia & Mortality Intensive Cardiac Unit 25 22.6% *Thrombolysis 20 15 10 5 0 P<0.001 8.0% 4.3% 3.2% 2.5% < 81 81-99 100-125 126-150 151-199 >199 n=62 n=123 n=280 n=186 n=200 n=196 Blood Sugar(mg/dL) 8.7% Pinto DS, et al. J Am Coll Cardiol. 2005;1:178-83.
Low Blood Sugar May Affect Heartbeat All volunteers monitored with a continuous glucose monitor for 5 days, as well as a 12-lead Holter monitor for heart activity. Overall, recorded 1,258 hours of time with normal blood sugar levels, 65 hours with high and 134 hours of low blood sugar The risk of a slow heart rate was 8 times higher when blood sugar was low at night compared to normal. Heller et al Diabetes Care 2014
GLUCOSE VARIABILITY PRE VILDAGLIPTIN POST PRE GLIMEPIRIDE POST
Heart Failure, Saxagliptin and Diabetes Mellitus: Observations from the SAVOR - TIMI 53 Randomized Trial saxagliptin treatment was associated with an increased risk for hospitalization for heart failure. This increase in risk was highest among patients with elevated levels of natriuretic peptides, prior heart failure, or chronic kidney disease Circulation. 2014 Sep 4.
HYPOGLYCEMIA according to medication Dashed & dotted SU Solid: idpp4 Diabetes Ther DOI 10.1007/s13300-014-0082-y
Hypoglycemia & Quality of Life Insomnia Circadian rhythm alterations Increased FBG for safety
The Gladiator Diet How to eat, exercise, and die a violent death "Gladiators needed subcutaneous fat, to be protected from cut wounds and shields nerves and blood vessels in a fight. Not only would a lean gladiator have been dead meat, he would have made for a bad show. Surface wounds look more spectacular Karl Grossschmidt The London Times 12/15/02
Financial Burden due to increased BW in DM2 Annual health burden due to the increased BW p<0.006 Increased BW Stable BW Total Health Cost 7.260 5.541 Diabetes Cost 2.141 1.869 Increased BW 1% Increased health cost 3,1% (213 USD) Yu et al, Current Med Res Opin 23(9):2157-69, 2007
Weight loss & BG Effect of BW loss on FBG in obesity with DM2 J Am Coll Nutrition. 2003;22(5):331 339
β cell & insulin resistance
islets-obesity-diabetes Butler et al, 2003 Diabetes 52:102-110 Post mortem autopsies
«SMART» THERAPEUTIC MEANS EFFICATIOUS SPECIFIC TARGET ADVERSE EVENTS PLEIOTROPIC EFFECT WELLCOMED
FDA.Aprooved
GUIDELINES????
GUIDELINE LIMITATIONS What is best for patients overall, as recommended in guidelines, may be inappropriate for individuals Should be shared decision making, not ignoring patients preferences
GUIDELINE LIMITATIONS Perspective may be recommended: to help control costs serve societal needs protect special interests (those of doctors, or politicians)
PHARMACEUTICAL EXPENSE FOR DM2 Laiko, Nikea, Tzanio 1998-2006 Liatis et al, Exp Clin Endo Diab 117:505-10, 2009
PHARMACEUTICAL EXPENSE 1998-2006 Liatis et al, Exp Clin Endo Diab 117:505-10, 2009
CONCLUSION newer medication : less frequent dosing less invasive delivery systems fewer side effects
LOOKING FOR HOPE Drug evolution is not revolutionary but establishes in a very low pace Blind controversy due to financial issues delays research and cancels the investigation of new ideas
FUNDAMENTALS DIET & EXERCISE