1. Silaja Cheruvu, R3

2.  What’s the BEST way to prevent diabetes in high risk patients?  By doing nothing?  With lifestyle changes?  With medication?

3.  27 centers  1996-1999  3234 participants  “High Risk” ◦ 25 years old ◦ BMI>24 ◦ Elevated fasting glucose, 2 hour GTT

4.  Placebo arm=Standard lifestyle recommendations  Metformin arm  Troglitazone arm (discontinued early)  Intensive Lifestyle Modification arm ◦ Achieve/maintain a 7% weight loss ◦ 150 minutes/week ◦ 16 week curriculum

5.  Placebo arm ◦ 77%  Metformin arm ◦ 72%  Intensive Lifestyle Modification arm ◦ 50% reached goal weight loss ◦ 38% kept the weight off ◦ 74% were exercising at 24 weeks ◦ 58% kept exercising

6.  Crude Incidence (person-years) ◦ Placebo: 11 ◦ Metformin: 7.8 ◦ ILM: 4.8  Cumulative Incidence (over 3 years) ◦ Placebo: 28.9 % ◦ Metformin: 21.7 % ◦ ILM: 14.4 %

7.  Incidence of DM was REDUCED by 31% (CI: 17-43) in metformin arm  Incidence of DM was REDUCED by 58% (CI: 48-66) in ILM arm  NNT ◦ Metformin: 13.9 (CI: 8.7-33.9) ◦ ILM: 6.9 (CI: 5.4-9.5)

8.  Were the patients randomized?  Was randomization concealed?  Were patients similar in prognostic factors? ◦ Table 1  Was the study blinded?  How complete was the follow-up?  Was the study stopped early?  Intention to treat?

9.  Absolute Risk Reduction ◦ ARR = CER – EER ◦ CER = 28.9% ◦ EER = 14.4%  ARR = 28.9% - 14.4% = 14.5% In those patients who are high risk for developing DM, when followed for 3 years, 14.3% fewer develop DM if they participate in ILM compared to placebo.

10.  Relative Risk Reduction ◦ RRR = (CER – EER ) /CER x 100 ◦ CER= 28.9 ◦ EER=14.4 ◦ (28.9% - 14.4%) / 28.9 % x 100 = 50% Over a 3 year period, there is a 50% decrease in the incidence of DM in ILM group when compared to the placebo group.

11.  Number Needed to Treat (ILM) ◦ NNT=1/ ARR ◦ 1/0.145 = 7  Number Needed to Treat (metformin) ◦ NNT=1/ARR ◦ 1/0.072 = 14 In order to prevent 1 case of DM over a 3 year period, you would have to treat 7 people with the intensive lifestyle modifications and 14 people with metformin.

12.  Confidence Intervals and Precision ◦ Number Needed to Treat  ILM: NNT=7 (CI: 5.4 to 9.5)  Metformin: NNT=14 (CI: 8.7 to 33.9) ILM arm is more precise than metformin arm but both are statistically significant.

13.  UNM, Shiprock and Zuni ◦ DIPS in Zuni  No subgroup analysis of high HbA1Cs vs low HBA1Cs  Subgroup analysis ◦ Metformin arm NOT statistically significant in Hispanics and Native Americans

14.  Good study BUT it’s a surrogate outcome  Only followed for 3 years… ◦ Blinded arm terminated early  Even with LOW adherence, ILM works! ◦ …but so does metformin!  POLICY CHANGE ◦ Can our patients exercise and do they access to healthy foods?