1. Importance of early glycemic control in management of type 2 diabetes
Prof. Khalifa M. Abdallah
Professor of Internal Medicine
Unit of Diabetes & Metabolic Diseases
Alexandria Faculty of Medicine

2. Overview The importance of early and sustained glycemic control
The rationale for early insulinization
Advantages of basal insulin therapy
Take home message

3. Diabetes Mellitus A Constellation of Complications
Gastropathy
Autonomic Neuropathy
Renal Disease
Peripheral Neuropathy
Retinopathy/ Macular Edema
Hypertension
Cardiovascular Disease
Dyslipidemia
Peripheral Vascular Disease
Erectile Dysfunction
Diabetes
Leading cause of adult blindness
Results in 2- to 4-fold increase in cardiovascular risk
Nearly double the rates of diagnosed depression
1,2,3 3

4. - A1c & Microvascular Complications 60 – 70 % Reduction of Complications
Retinopathy 15
Nephropathy 13 11 9
Neuropathy
Relative Risk 7
The relative risk of developing microvascular complications of diabetes (progression of retinopathy, progression to clinical neuropathy, progression to severe nonproliferative or proliferative retinopathy, or progression to microalbuminuria) was directly related to HbA1c level. In this representation of the relationship between the risk of complications and HbA1c, the relative risk of complications is set to 1 at an HbA1c of 6%.
Reference
Skyler J. Diabetic complications. The importance of glucose control. Endocrinol Metab Clin. 1996;25:243–254. 5
Microalbuminuria 3 1 6 7 8 9 10 11 12
HbA1c (%)
Skyler JS. Endocrinol Metab Clin. 1996;25:243–254.

5. Effects of reduction of A1c by 1.9% in intensively treated group
Risk Reduction in DCCT
Effects of reduction of A1c by 1.9% in intensively treated group
Neuropathy
Albuminuria
Retinopathy
76%
54%
60%
39%
Onset
Progression 20 40 60 80
albuminuria
Risk Reduction
P=0.002
P=0.002
P=0.002
P=0.04
P=0.04
DCCT Research Group. N Engl J Med. 1993;329:

6. A1c : Myocardial Infarction and Microvascular Complication80
Microvascular disease 60
Myocardial infarction
Incidence per 1000 patient-years 40 20
Mean HbA1c (%) 5 6 7 8 9 10 11
UKPDS 35. BMJ 2000; 321:

7. UKPDS: Glucose Control Study Summary
The intensive glucose control policy maintained a lower HbA1c by a mean of 0.9% over a median follow up of 10 years from diagnosis of type 2 diabetes with reduction in risk of:
12% for any diabetes related endpoints p=0.029
25% for microvascular endpoints p=0.0099
16% for myocardial infarction p=0.052

8. UKPDS: Glucose Control Study Summary
The intensive glucose control policy maintained a lower HbA1c by a mean of 0.9% over a median follow up of 10 years from diagnosis of type 2 diabetes with reduction in risk of:
12% for any diabetes related endpoints p=0.029
25% for microvascular endpoints p=0.0099
16% for myocardial infarction p=0.052

9. Causes of Death in People With Diabetes50
65%
of Diabetic Patients Deaths
are from CV Causes
Deaths (%) 40 40 30 20 15 13 13 10 10 4 5
All other
Diabetes
Malignant neoplasms
Other heart disease
Pneumonia/
influenza
Ischemic
heart disease
Cerebrovascular disease
WHO Report World Health Organisation. Geneva 1997

10. Can long-term glycemic control reduce the risk of cardiovascular disease?

11. Summary of ACCORD, ADVANCE and VADT
No. of participants
10,251
11,140
1791
Participant age ,years 62 66 60
HbA1C at Baseline, %
8.1
7.5
9.4
Significant Effect on Macrovascular Outcomes? No
Significant Effect on Microvascular Outcomes? NA
Significant for nephropathy, not retinopathy
Rosiglitazone use, (intensive vs. standard)
90% vs. 58%
17% vs. 11%
85% vs. 78%
Duration of follow-up, years
3.4
5.0 6

12. ACCORD ADVANCE and VADT- No Significant Effect on Macro or Micro Vascular Outcomes
No. of participants
10,251
11,140
1791
Participant age ,years 62 66 60
Duration of diabetes at study entry, years 10 8
11.5
HbA1C at Baseline, %
8.1
7.5
9.4
Participants with prior cardiovascular event, % 35 32 40
Duration of follow-up, years
3.4
5.0 6

13. DCCT / EDIC: majority of patients receive intensive therapy and HbA1C levels converge
Conventional
Conventional
Conventional
Conventional group
Conventional group
Conventional group 11 11
encouraged to switch
encouraged to switch
encouraged to switch
to intensive
to intensive
to intensive 10 10
treatment
treatment
treatment
(%)
(%) 9 9 c c 1 1 8 8
HbA
HbA
During DCCT, intensive insulin therapy in people with type 1 diabetes significantly reduced HbA1c relative to those receiving conventional treatment. The intensively-treated group achieved a mean HbA1c of 7.1%, while the conventionally-treated patients had HbA1c of approximately 9.0%. During the EDIC (Epidemiology of Diabetes Intervention and Complications research group) follow-up of the DCCT cohort, all patients were encouraged to adopt intensive insulin therapy. During this time, HbA1c stablised to a similar level (just over 8%) in both treatment groups. 7 7 6 6 1 1 2 2 3 3 4 4 5 5 6 6 7 7 8 8 9 9
DCCT
DCCT 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5 6 6 6 7 7 7
DCCT
DCCT
end
end
EDIC
EDIC
EDIC
Year
Year
DCCT/EDIC: NEJM, 2005;353, No 25:

14. DCCT / EDIC – incidence of all predefined cardiovascular outcome
Patients previously receiving intensive treatment in the DCCT study had a 57% reduced incidence of nonfatal myocardial infarction, stroke or death from cardiovascular disease
DCCT/EDIC: NEJM, 2005;353, No 25:

15. UKPDS: Post-Trial Changes in HbA1c
Mean (95%CI)
UKPDS results presented
UKPDS 80. N Eng J Med 2008; 359

16. UKPDS: Legacy Effect of Earlier Glucose Control
After median 8.5 years post-trial follow-up
Aggregate Endpoint
Any diabetes related endpoint RRR: 12% 9% P:
Microvascular disease RRR: 25% 24% P:
Myocardial infarction RRR: 16% 15% P:
All-cause mortality RRR: 6% 13% P:
RRR = Relative Risk Reduction, P = Log Rank
N Eng J Med 2008

17. Can long-term glycemic control reduce the risk of cardiovascular disease?
Yes
If early and sustained glycemic control started
before atherosclerosis is established

18. At present, The question is not whether to intensively treat people with type 2 diabetes at onset of the disease to prevent long-term complications. The question rather is how to intensively treat patients with type 2 diabetes to consistently keep A1c < 7% all through the course of the disease

19. ADA: Position statement: Need for early treatment
“Patients with shorter duration of
Type 2 diabetes and without
established atherosclerosis might
reap cardiovascular benefits
from intensive glycaemic control”1
Skyler JS, et al. J Am Coll Cardiol. 2009;53(3):

20. Glycemic control & A1c Target
AACE
ADA
<6.5
<7
A1c (%)
<110
80-120
Preprandial (mg/dl)
<140
Postprandial (mg/dl)
Bedtime (mg/dl)
ADA: American Diabetes Association
AACE: American Association of Clinical Endocrinologists

21. Two-thirds of Type 2 Patients are not Achieving Glycemic Control
R19/p19/C1/P1/L1-4
NHANES1
44.5%
35.8%
A1c <7%
R1/p3/L1-2
N=1215
N=372
AACE survey
Only about one-third of Americans with type 2 diabetes meet either the ADA or AACE standards for glycemic control.
Recent statistics reveal that the majority of patients with diabetes are not achieving adequate glycemic control. The National Health and Nutrition Examination Survey (NHANES) is conducted periodically on a nationwide scale in the United States to gather health and nutritional data. Results from the survey revealed that 44.5% of patients with type 2 diabetes had an A1c level of 7% or lower. NHANES data gathered during are even more disappointing: just over one-third of patients reported having an A1c level of 7% or lower.
The NHANES findings are corroborated by data gathered during by the American Association of Clinical Endocrinologists (AACE). In a survey of 157,000 patients with type 2 diabetes across 39 states in the US, two-thirds of respondents were failing to achieve an A1c goal of 6.5% or below.
References:
Koro CE, Bowlin SJ, Bourgeois N, Fedder DO. Glycemic control from 1988 to 2000 among U.S. adults with type 2 diabetes. Diabetes Care 2004;27:17-20.
American Association of Clinical Endocrinologists. “State of Diabetes in America,” Available at: Report.pdf. Accessed January 6, 2006.
33%
R19/p19/C1/P1/L1-4
A1c 6.5%
N=157,000 type 2 patients 39 US states included
R1/p3/L1-2
NHANES = National Health and Nutrition Examination Survey.
1Koro et al. Diabetes Care. 2004;27:17-20; 2 “State of Diabetes in America,” American Association of Clinical Endocrinologists, Available at: DiabetesAmericaReport.pdf. Accessed January 6, 2006.

22. Traditional Type 2 Diabetes Management: A “Treat-to-Fail Approach”
Published Conceptual Approach
Mean HbA1c of patients
1/Del Prato
p.1349 Figure 2A
2/Campbell
p.626 Figure 1
OAD +
multiple daily
insulin injections
Diet and exercise
OAD
monotherapy
OAD up-titration
OAD
combination
OAD +
basal insulin 10 9 8
HbA1c Goal 7 6
Duration of Diabetes
Conventional stepwise treatment approach
OAD=oral antihyperglycemic agent.
Adapted from Campbell IW. Need for intensive, early glycaemic control in patients with type 2 diabetes. Br J Cardiol. 2000;7(10):625–631. Del Prato S et al. Int J Clin Pract. 2005;59:1345–1355.

23. Delays often occur between stepping up from monotherapy to combination therapy
Length of time between first monotherapy HbA1c > 8.0% and switch/addition in therapy (months) 25
20.5 months 20
14.5 months 15
Months 10
Initial improvements in glycemic control seen with conventional antidiabetic agents in monotherapy are usually not maintained long term, and most patients ultimately require combination therapy to achieve good glycemic control.1
In practice, there is often a considerable delay between the loss of glycemic control with monotherapy and the introduction of another antidiabetic agent.
Analysis of data from the Kaiser Permanente Northwest database
(1994–2002)2 found that the average time from when the HbA1c action point of 8% was exceeded and the introduction of an additional or alternative oral antidiabetic agent was:
14.5 months for those on metformin monotherapy
20.5 months for those on sulfonylurea monotherapy.
Earlier introduction of combination therapy could reduce exposure of patients to the risk of diabetes-related complications associated with periods of hyperglycemia.2
1Turner RC, et al. JAMA 1999; 281:2005– Brown, JB et al. Diabetes Care 2004; 27:1535–1540. 5
Metformin only
Sulfonylurea only
n = 513
n = 3394
Brown, JB et al. Diabetes Care 2004; 27:1535–1540.

24. Clinical Inertia: Failure to Advance Therapy When Required
Percentage of subjects advancing when A1C >7% < 8%
At insulin initiation, the average patient had:
100
5 years with A1C > 8%
10 years with A1C > 7% 80
66.6% 60
44.6%
% of Subjects
35.3% 40
18.6% 20
Diet
Sulfonylurea
Metformin
Combination
Brown JB et al. Diabetes Care 2004;27:

25. Lifestyle Intervention + Metformin
Diagnosis
Lifestyle Intervention + Metformin No
HbA1c ≥7%
Yes
Add
Basal Insulin
Add
Sulfonylurea
Add
Glitazone
Add
DPP-4 inhibitor
ADA-EASD-Consensus 2006

27. Consensus Algorithm Update 2009
Tier 1: Well-validated core therapies
Lifestyle + Metformin
plus
Basal Insulin
At diagnosis:
Lifestyle + Metformin
Lifestyle + Metformin
plus
Intensive Insulin
Lifestyle + Metformin plus
Sulfonylureaa
Step 1
Step 2
Step 3
Tier 2: Less well-validated therapies
Check A1C every 3 months until <7%. Change treatment if A1C is ≥7%
Lifestyle + Metformin plus
Pioglitazone
No hypoglyceamia
Oedema / CHF
Bone Loss
Lifestyle + Metformin plus
Pioglitazone plus Sulfonylurea
Lifestyle + Metformin plus
GLP-1 agonist
No hypoglyceamia
Weight loss
Nausea / vomiting
Lifestyle + Metformin plus
Basal Insulin
Nathan DM et al. Diabetes Care 2009;32:

28. Sulphonylureas failed to maintain glycemic control
Glyburide 1
Glimpiride
Glyburide
Glibenclamide
Gliclazide
Glyburide
Hanefeld (n=250)
HBA1c % Reduction -1
Tan (n=297)
Chicago (n=230) -2
Periscope (n=181)
ADOPT (n=1441)
UKPDS (n=1573) 1 2 3 4 5 10
Time (years)

29. UKPDS: Islet -cell function and the progressive nature of diabetes
Time of diagnosis
100 80 60
(% of normal by HOMA)
Islet -cell function
Pancreatic function
= 50% of normal 40 20
10 9 8 7 6 5 4 3 2 1 1 2 3 4 5 6
Years
HOMA = homeostasis model assessment
Holman RR. Diab Res Clin Pract. 1998;40(suppl):S21-S25;
UKPDS. Diabetes. 1995;44:

30. Advantages of insulin
It lowers mean blood glucose in a predictable dose-dependent manner
Can be tailored to individual needs on a unit-to-unit basis
It has the longest experience than any other drug (90 years)
No contraindications to its use

31. Advantages of insulin
Insulin is the only drug that directly reduces lipolysis and free fatty acid concentrations in blood, thus reducing lipotoxicity
Insulin improves lipoprotein metabolism, decreases LDL cholesterol and triglycerides, and increases HDL cholesterol
Insulin improves endothelial dysfunction

32. thoughts/concerns about starting insulin
Common Fears:
Needles
Hypoglycemia
Weight gain
Common Beliefs:
Insulin is the last option
Insulin causes complications
Insulin is a personal failure
Adverse impact on relationships/lifestyle 32

33. What should I tell people with Type 2 diabetes about insulin?
‘Most people with Type 2 diabetes eventually need insulin because their own production of insulin falls off with time and they therefore inevitably become insulin deficient’

34. What should I tell people with Type 2 diabetes about insulin?
‘If you need insulin, it doesn’t mean you failed. Tablets cannot control blood glucose forever, because they don’t stop the problem of your own declining insulin production getting worse’
Islet -cell dysfunction worsens over time, regardless of therapy

35. What should I tell the person with Type 2 diabetes who needs insulin, but doesn’t want to take it?
‘Insulin will not make your diabetes worse. In fact, it will help control your glucose, so you’ll have fewer complications and you’ll feel better.’
Strict glycaemic control reduces the risks of both microvascular and macrovascular complications

36. Insulin Regimens
1. Basal insulin ( NPH or long-acting insulin analogue) + OAD
2. Total insulin replacement therapy
- Premixed insulins
- Basal-bolus

37. 24-hour Plasma Glucose Curve: Rationale for Adding Basal Insulin
Slide 1-22
400
Diabetes
300
Glucose (mg/dL)
200
Normal
100
0600
1000
1400
1800
2200
0200
0600
Time of Day
Adapted from Polonsky KS et al. N Engl J Med. 1988;318:

38. 24-hour Plasma Glucose Curve: Rationale for Adding Basal Insulin
Slide 1-22
400
300
Diabetic
Glucose (mg/dL)
200
100
Normal
0600
1000
1400
1800
2200
0200
0600
Time of Day
Adapted from Polonsky KS et al. N Engl J Med. 1988;318:

39. Starting With Basal Insulin in DM 2 – Advantages
1 injection with no mixing
Insulin pens for increased acceptance
Slow, safe, simple titration
Low dosage
Effective improvement in glycemic control
Limited weight gain
Slide 6-37
INSULIN TACTICS
Starting With Basal Insulin
Advantages
Patients who no longer respond adequately to oral agents will benefit from combination therapy that consists of maintaining the use of oral antidiabetic agents together with insulin therapy. The advantages of adding basal insulin to prior treatment with oral agents include the following: (1) only one insulin injection may be required each day, with no need for mixing different types of insulin; (2) the use of insulin pens can enhance patient acceptance of the treatment; (3) titration can be accomplished in a slow, safe, simple fashion; and (4) eventually combination therapy requires a lower total dose of insulin. The result is effective improvement in glycemic control while causing only limited weight gain.

40. Insulin Glargine vs. NPH Insulin Added to Oral Therapy
Mean A1C Levels During Study 9
Insulin glargine
NPH insulin 8
Mean A1C (%) 7
Target A1C (%) 6 4 8 12 16 20 24
Time (weeks)
Riddle MC et al. Diabetes Care. 2003;26:

41. Less Hypoglycemia with Insulin Glargine vs NPH
3500
3000
2500
2000
1500
1000
NPH
Insulin glargine
Hypoglycemia events per 100 patient-years
T1DM
p=0.004 between treatments
HbA1c
200
150
100 50
Hypoglycemia events per 100 patient-years
T2DM
p=0.021 between treatments
HbA1c
Mullins P et al. Clin Ther 2007;29:1607−19.

42. Insulin Glargine vs. NPH Insulin Added to Oral Therapy
Symptomatic Hypoglycemia by Time of Day
Glargine
NPH insulin
Basal insulin
1.4 * *
1.2 * *
1.0 * *
0.8 *
Events per Patient-Year
0.6
0.4
0.2
Similar trends were observed when the overall number of symptomatic hypoglycemic episodes occurring over time were analyzed.
Between midnight and 8 am, and breakfast time, there were fewer episodes of symptomatic hypoglycemia in the insulin glargine group compared with the NPH insulin group
At other times of day, the number of episodes of symptomatic hypoglycemia were similar in both treatment groups
ROSENSTOCK Abstract
OBJECTIVE: To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone. RESEARCH DESIGN AND METHODS: A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily in = 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose <6.7 mmol/l. At study end point, the median total daily insulin dose in both treatment groups was 0.75 IU/kg. RESULTS: The treatment groups showed similar improvements in A1C from baseline to end point on intent-to-treat analysis. The mean change (means +/- SD) in A1C from baseline to end point was similar in the insulin glargine group ( /- 0.1%) and the NPH group ( /- 0.1%) after patients began with an average baseline A1C of approximately 8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.%) However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase(26.5 vs. 35.5%, P = ). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P < ). CONCLUSIONS: In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine demonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin. 20 22 24 2 4 6 8 10 12 14 16 18
Time of Day (hour)
Hypoglycemia defined as PG  72 mg/dL, by hour
*P < 0.05 vs. glargine.
Riddle MC et al. Diabetes Care. 2003;26:

43. Insulin Glargine Trials Showing Effective Reduction in HbA1c10 9 8 7 6 5
9.5
8.85
8.80
8.71
8.80
8.61
HbA1c (%)
7.14
7.15
7.14
6.96
6.96
6.80
Treat-To-Target
LANMET
APOLLO
LAPTOP
Triple Therapy
INITIATE
Baseline
Study endpoint

44. Insulin Glargine Plus OADs vs Twice-daily Premixed 70/30 Human Insulin
Treatment Regimen
Target: FPG 100 mg/dL
Subjects (n=364) were randomly assigned to:
Insulin glargine once daily + continued OADs
OADs*
Premixed human insulin 70/30 BID
Time (wk)
Baseline
End Point
*Sulfonylurea + metformin
OAD=oral antidiabetic drug
Janka HU, et al. Diabetes Care. 2005;28:

45. Insulin Glargine Plus OADs vs Twice-daily Premixed Human Insulin
Change in A1C from Baseline to Study End Point*
P=0.0003
Baseline
24 week
A1C
At 24 weeks, superior reduction was achieved with insulin glargine plus OADs compared with twice-daily pre-mixed insulin.
*Intent-to-treat analysis
OAD=oral antidiabetic drug
Janka HU, et al. Diabetes Care. 2005;28:
Janka H, Plewe G, Kliebe-Frisch C, et al. Starting insulin for type 2 diabetes with insulin glargine added to oral agents vs twice-daily premixed insulin alone. Presented at: American Diabetes Association 64th Scientific Sessions; June 4-8, 2004; Orlando, Fla.

46. LAPTOP: Insulin Glargine Versus 70/30 Premixed Insulin in OHA Failures
N=371 insulin-naïve patients Insulin glargine + OADs vs twice-daily human NPH insulin (70/30) Follow-up: 24 weeks
Twice-daily premixed insulin
Insulin glargine + OADs
p=0.0003 9 5
5.7
1.3%
1.7% 4 8
p=0.0009 3
7.5%
Hypoglycaemia* (events/patient year)
HbA1c (%) 7
7.2%
2.6 2 6 1 5
*Confirmed symptomatic hypoglycaemia (blood glucose <60 mg/dl [<3.3 mmol/l])
Janka H et al. Diabetes Care 2005;28:254−259.

47. Documented Hypoglycemic Episodes Per Patient-Year
Less Hypoglycemia With Glargine Plus OADs vs Twice-daily Premixed 70/30 Human Insulin
Documented Hypoglycemic Episodes Per Patient-Year
P<0.0001 10
9.9 8
# of Episodes
Per
Patient-Year 6 4
4.1
At 24 weeks, less hypoglycemia was documented with insulin glargine plus oral anti-diabetic drugs versus twice-daily pre-mixed insulin. 2
Insulin Glargine + OAD
Premixed
Average dose = 28.2 IU with G + OAD vs 64.5 IU with premixed insulin
Weight Gain: 1.4 ± 3.4 kg with G + OAD vs 2.1 ± 4.2 kg with pre mixed insulin
Janka HU, et al. Diabetes Care. 2005;28:
Janka H, Plewe G, Kliebe-Frisch C, et al. Starting insulin for type 2 diabetes with insulin glargine added to oral agents vs twice-daily premixed insulin alone. Presented at: American Diabetes Association 64th Scientific Sessions; June 4-8, 2004; Orlando, Fla.

48. Conclusions
Due to declining -cell function, insulin therapy will be necessary for most patients with Type 2 diabetes
Insulin therapy should be initiated early when glycemic control exceeds the recommended targets
Insulin effectively lowers HbA1c, thereby reducing the risks of both micro- and macrovascular complications

49. Relative Contributions of Fasting and Postprandial Glycemia(%) to The Overall Diurnal Hyperglycemia Over Quintiles of A1C
PPG
FPG
100 80 70 70
Contribution % 60 40 30 30 20
A1c <7%
A1c 8%
A1c 9%
A1c >10%
Diabetes Care 2003, 26:

50. Conclusions-cont.
Insulin glargine when used as a basal insulin has the following advantages:
It effectively lowers fasting and mean blood glucose
Easily initiated and titrated
Low risk of hypoglycemia

51. Thank You

52. Insulin glargine provides superior long term efficacy vs. NPH.
Insulin glargine offers long-term efficacy without the need for intensification
Key points
Insulin is normally added to oral glucose-lowering drugs in people with type 2 diabetes when glycaemic control becomes suboptimal.
Outcomes in people starting insulin therapy with neutral protamine Hagedorn (NPH), detemir, glargine or premixed insulins were evluated
Insulin-naive people with type 2 diabetes (n = 8009), ‡ 35 years old, HbA1c ‡ 6.5% and begun on NPH (n = 1463), detemir (n = 357), glargine (n = 2197) or premix (n = 3992), were identified from a UK database of primary care records (The Health Improvement Network)
Unadjusted and multivariate-adjusted analyses were conducted, with persistence of insulin therapy assessed by survival analysis.
In the study population (n = 4337), baseline HbA1c was 9.5 ± 1.6%, falling to 8.4 ± 1.5% over 12 months (change )1.1 ± 1.8%, p < 0.001)
Compared with NPH, people taking detemir, glargine and premix had an adjusted reduction in HbA1c from baseline, of 0.00% (p = 0.99), 0.19% (p < 0.001) and 0.03% (p = 0.51).
Body weight increased by 2.8 kg overall (p < 0.001), and by 2.3, 1.7, 1.9, and 3.3 kg on NPH, detemir, glargine and premix (p < for all groups)
Insulin dose at 12 months was 0.70 (overall), 0.64, 0.61, 0.56 and 0.76 U ⁄ kg ⁄ day
After 36 months, 57% of people on NPH, 67% on glargine and 83% on premix remained on their initially prescribed insulin
In routine clinical practice, people with type 2 diabetes commenced on NPH experienced a modest disadvantage in glycaemic control after 12 months compared with other insulins.
When comparing the insulins, glargine achieved best HbA1c reduction, while premix showed greatest weight gain and the highest dose requirement, but had the best persistence of therapy
Insulin glargine provides superior long term efficacy vs. NPH.
Gordon J, et al. Int J Clin Pract. 2010;64(12):   52 52