t2d initial oral therapy Flashcards
Pharmacologic Interventions match the trials to the drug Diabetes Prevention Program (DPP) Stop NIDDM acarbose – Lancet 2002;35 ACT Now (DREAM)
metformin acarbose pioglitazone Diabetes REduction Assessment with ramipril and rosiglitazone Medication
4 of 5 agents tested reduce the risk of progressing
from pre-diabetes to type 2 diabetes
which 4
– Metformin (DPP) 31% Risk Reduction
– Acarbose (Stop NIDDM) 25% Risk Reduction
– Pioglitazone (ACT Now) 72% Risk Reduction
– Rosiglitazone (DREAM) 62% Risk Reduction
– Ramipril (DREAM) no significant differenc
HOWEVER
– Are we preventing type 2 diabetes, or just starting therapy at a lower threshold of disglycemia?
– What are the long-term benefits of initiating treatment during pre-diabetes?
– Are the benefits worth the adverse effects?
see slide 11 + MOA of drugs
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Goals of Therapy – Type 2 Diabetes
• Reduce the risk of microvascular and
macrovascular complications of diabetes
• Maintain glycemic treatment targets
– A1c (for most adults) <7.0%
– Fasting and pre-meal blood glucose 4-7 mmol/L
– 2-hour post-prandial blood glucose 5-10 mmol/L
• Minimize the risk of hypoglycemia
• Maintain treatment targets for cardiovascular
risk factors
Pharmacotherapy in Type 2
Diabetes Checklist
- CHOOSE initial therapy based on glycemia
- START with metformin +/- others
- INDIVIDUALIZE your therapy choice based on characteristics of the person with diabetes and the agent
- REACH TARGET within 3-6 months of diagnosis
- Healthy behaviour interventions should be
____________ [Grade B, Level 2]. Metformin
may be used at the time of diagnosis, in
conjunction with healthy behaviour interventions
[Grade D, Consensus]
intiated at diagnosed
Lifestyle does not stop progression - Not the best evidence Not as good as you think Overtime, adherence to lifestyle wears off Need to move on to metformin
- If glycemic targets are not achieved using healthy
behaviour interventions alone within 3 months,
___________ should be added to
reduce the risk of _____________
[Grade A, Level 1A]. Metformin should be chosen
over other agents due to its low risk of
hypoglycemia and weight gain [Grade A, Level 1A],
and long-term experience [Grade D, Consensus].
antihyperglycemic therapy
microvascular complications
Can try for 3 months, if it doesn’t work need to start metformin
Need to make sure it is down in the 3 months or choose other agents to help
Metformin, low risk of hypoglycemic event and weight neutral
Some reduce weight, cheap
If A1C values are _________at diagnosis,
initiating metformin in combination with a second
antihyperglycemic agent should be considered to
increase the likelihood of reaching target [Grade B, Level 2]
≥1.5% above target
- Individuals with ___________(e.g.,
marked hyperglycemia, ketosis or unintentional
weight loss) should receive insulin with or without
metformin to correct the relative insulin deficiency
[Grade D, Consensus]
metabolic decompensation
Severe hypoglycemia
In hospital setting, start insulin as short term bridge
May or may not start metformin
A1C <1.5% over target
Initiate healthy behavior interventions and start metformin if not at target in 3 months OR Start metformin with healthy behavior interventions
Assess at 3-6 months, see where they are
If not at goal, increase dose of medication
If already on metofrmin and not in goal, add on second agent (don’t stop metformin), 3rd agent
Rarely take away
A1C ≥ 1.5% over target
Start metformin with healthy behavior interventions AND Consider second concurrent agent
Initial choice of therapy
Symptomatic Hyperglycemia and/or Metabolic Decompensation
Polyuria
• Polydipsia
• Weight loss
• Volume depletion
start insulin +/- metformin
Why is Metformin the Initial Agent?
• Efficacy in lowering A1c • Favourable side effect profile – Hypoglycemia risk is negligible – Weight gain is minimal or neutral • Affordable • Clinical trial evidence of benefit – UK Prospective Study (newly diagnosed T2DM)
- Some reductions of any diabetes endpoint
Caveat is there weren’t a lot of pt using metformin
– SPREAD-DIMCAD (T2DM & CAD)2
• 304 patients randomized to metformin or glipizide for ≥3 years
• After a median follow-up 5.0 years, primary outcome of death, MI, stroke, or revascularization was lower in metformin group
(HR: 0.54; 95% CI 0.30-0.90
Reappraisal of Metformin Efficacy
Meta-analysis of RCTs
Cautions: of the 12 studies contributing data to these analyses,
7 followed patients for ≤12 months
7 were primarily designed to measure glycemic response
7 observed ≤5 events
Alternatives to Initiating Type 2
Diabetes Therapy with Metformin
• Intolerance or contraindications to metformin
• Intolerance or contraindications to metformin
– Gastrointestinal side effects (nausea, vomiting,
flatulence, abdominal discomfort)
– Metallic taste
– Risk of lactic acidosis*
– Renal impairment (eGFR <30 mL/min/1.73 m2)
• Alternatives: Sulfonylureas, DPP4 inhibitors,
SGLT2 inhibitors, GLP1ras
Used routiely in eGFR <60
Some drs use it <15, 20
