Diabetes: T2DM - In the news 2009
Insulin Glargine: does it increase cancer risk?
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No conclusive proof but being investigated after results of 3 or 4 observational trials raise possibility. See Rapid Rx: http://www.rxfiles.ca/rxfiles/uploads/documents/Diabetes-Glargine-cancer-RapidRx-10Jul09.pdf |
RECORD trial: rosiglitazone AVANDIA & CV risk:
n=4447, ~ 5.5yr; T2DM (A1C mean ~ 7.9%ð7.4-7.9%); non-inferiority trial; open label; funded by GSK
metformin or sulfonylurea (SU) + rosiglitazone vs metformin + SU. No difference in CV death, MI; increase rate of HF & fracture. Suggests that CV outcomes for rosiglitazone are similar (e.g. no worse) to metformin + a SU over 5.5 yrs. However limitations include open label design, more of the rosi group on statins & high rate of dropouts.
Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ; RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009 Jun 20;373(9681):2125-35.
See RxFiles Trial Summary at: http://www.rxfiles.ca/rxfiles/uploads/documents/Diabetes-RECORD-Trial-Summary.pdf Other Links: http://www.ncbi.nlm.nih.gov/pubmed/19501900 ; http://www.medscape.com/viewarticle/704038
CMAJ: CV Risk and Glycemic Control (Apr 28, 2009): http://www.cmaj.ca/cgi/reprint/180/9/907
CMAJ: Insulin analogues (Feb 17, 2009): (based on COMPUS systematic reviews)
1) Singh SR, Ahmad F, Lal A, et al. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ 2009;180(4):385-97. Online at: http://www.cmaj.ca/cgi/reprint/180/4/385 2) Cameron CG, Bennett HA. Cost-effectiveness of insulin analogues for diabetes mellitis. CMAJ 2009;180(4):400-7. http://www.cmaj.ca/cgi/reprint/180/4/400 . 3) Siebenhofer-Kroitzsch A, Horvath K, Plank J. Insulin analogues: too much noise about small benefits. CMAJ. 2009 Feb 17;180(4):369-70. http://www.cmaj.ca/cgi/reprint/180/4/369
ADA, ACC & AHA Position Statement - Intensive Glycemic Control & the prevention of CV Events - Jan/2009 Implications of ACCORD, ADVANCE & VA Diabetes Trials (ePublished - accessed Dec 30, 2008) - http://care.diabetesjournals.org/misc/finaldc9026.pdf ; or http://care.diabetesjournals.org/cgi/reprint/32/1/187 ;
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See also: Woo V. Important differences: Canadian Diabetes Association 2008 clinical practice guidelines and the consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2009 Mar;52(3):552-3; author reply 554-5. |
Diabetes: T2DM - In the news 2008
ADA / IDF – T2DM Update – Consensus Statement Dec 2008 (web Oct 2008)
Link to original pdf: http://care.diabetesjournals.org/misc/MedicalManagementofHyperglycemia.pdf or http://care.diabetesjournals.org/cgi/reprint/32/1/193
Key Observations:
A1C target left at <7%
Tier 1, Step 1: lifestyle + metformin; Tier 1, Step 2: add insulin or sulfonylurea (consider early insulin)
Tier 2: pioglitazone, exenatide (less well validated options than Tier 1)
Panel unanimously advised against using rosiglitazone (Avandia)
Comment on sitagliptin (Januvia): long term safety not established; expensive. Not included in Tier 1 or 2.
Highlights:
Targets
· DCCT & UKPDS: neither trial able to achieve goals in nondiabetic range (mean levels over time of ~7%)
· Target A1C: ADA < or = 7%; IDF: <6.5%; (None show intensive benefit on CVD outcomes; hope for fewer complications)
Selection of Drugs for T2DM
· Little to demonstrate clear superiority. Sorted into Tiers based on evidence & safety
Tier 1 – well validated
· Step 1: Lifestyle, metformin
· Step 2 + insulin; or + SU (consider insulin early)
Tier 2 – less well validated
· Tier 2: TZDs (pioglitazone); exenatide
Other alternatives after Tiers 1 & 2:
· Acarbose; Glitinide (repaglinide); sitagliptin
Lifestyle: wt loss of 4kg useful
Meds:
· A1C >8.5% need more BG lowering or combination treatments
· A1C < 7.5% agents with lesser BG potential ok
Metformin: rate of lactic acidosis only about 1/100,000; OK to use in reduced renal function (GFR CI if <30ml/min); titrate gradually over 1-2mo
SU: use at up to ½ maximum recommended dose which still has majority of effect
Acarbose: 25-45% discontinue due to adverse gastrointestinal; reduces CV outcomes STOP-NIDDM
TZD: unanimously advise against use of rosiglitazone Avandia due to uncertain neutral or worse cardiovascular outcomes
Sitagliptin / Januvia comment: lowers A1C 0.5 - 0.8; long term safety not established; expensive
Insulin
· No max; large doses may be necessary in some (>1unit/kg)
· A1C: RAIA & LAIA ----- no better on A1C lowering than conventional
· Severe hypoglycaemia: 1-3 cases / 100 patient-years
· Long-acting insulin analogues: modestly lower hypoglycemia risk compared to NPH
· Start NPH at HS or LAIA in AM
- (10 Units or 0.2units/kg)
· Adjust 2 units q3days till (FPG 3.9-7.2);
- 4 units q3days if FPG >10
· If Hypoglycemia or FPG <3.9, decrease by 4 units or 10%
· If A1C > or = 7%
- FPG in target in 2-3 months, check pre-prandial & consider 2nd dose of insulin
· If A1C increased, check 2hr PPG; consider adjust preprandial insulin
SMBG: fasting & pre-prandial (initial)
· Only necessary with insulin and secretagogues (SU & glitinides)
· Postprandial if A1C remains up
Algorithm: individualization
· Insulin often preferred over 3rd agent
· Insulin + MF a good combination
Other: if severely uncontrolled: FPG > 13.9; Random PG > 16.7; A1C >10%, question if type 1; or severe insulin deficiency
ADA = American Diabetes Association
ACC= American College of Cardiology Foundation
AHA= American Heart Association