1. Early Initiation of Insulin: Basal Bolus versus Premixed

2. ADA Diabetes Management Algorithm 2015

11. Need for Early and aggressive treatment

13. Legacy effect: early vs late glycemic control and complications risk
Aggressive glycemic control:
In Early stage T2 DM
‘Modestly reduced macro-vascular complication risk while posed additional complication’
Inzucchi et al., 2012; Skyler, Bergenstal, Bonow, et al., 2009, Stratton IM et al. BMJ 2000;321:405–412

14. Insulin at Diagnosis
AACE and the Canadian Diabetes Association suggest considering insulin treatment at the time of T2DM diagnosis if glycemic control is very poor (HbA1c levels >9%)
ADA/EASD guidelines recommend insulin therapy be considered for patients who present for the first time with T2DM and an HbA1c level >10%.
Handelsman, Y. et al. Endocr. Pract.17 (Suppl. 2), 1–53 (2011).
Bhattacharyya, O. K. Can. Fam. Physician. 55, 39–43 (2009).

15. Early Insulinization is Recommended by the ADA/EASD to Avoid Clinical Inertia
If HbA1c targets are not achieved after ~3 months of initial treatment, alternative therapy such as basal insulin should be initiated1,2
Early insulin therapy has the potential to achieve near-normal glucose control & prevent progression of glucose intolerance3
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes
1. Inzucchi SE, et al. Diabetologia 2012;55:1577–96
2. Nathan DM, et al. Diabetes Care 2009;32:193–203
3. ORIGIN Trial Investigators. N Engl J Med 2012;367:319–28

16. The legacy of basal insulin
Treat-To-Target Concept has demonstrated the role of basal insulin analogs in facilitating early insulin replacement, lower risk of hypoglycemia and becoming foundation of the therapy.
4T study also showed that, over the longer term (3 years), a premixed insulin regimen was not as effective as basal insulin at attaining glycemic targets.
People initiating insulin
treatment with basal insulin experienced significantly lower
rates of hypoglycaemia and less weight gain compared with
prandial and premixed insulin regimens. Thus, this study
provided the first clear evidence in favour of starting insulinbased
treatment with basal insulin
Diabetes Care in 2012: Current Trends and Future Directions

17. Differential effects of basal vs prandial insulin components of dysglycemia, body weight and hypoglycemia risk: the 4T study
4-T Study: Insulins Relative Changes over 3 Years and Hypoglycaemia
N Engl J Med 2009; 361:

18. Overview of Main Results
Biphasic
Prandial
Basal
Median HbA1c level achieved +
HbA1c targets achieved ++
Mean SMBG level achieved
Fewer hypoglycaemic episodes
+++
Less weight gain
Less increase in waist circumference
People initiating insulin
treatment with basal insulin experienced significantly lower
rates of hypoglycaemia and less weight gain compared with
prandial and premixed insulin regimens. Thus, this study
provided the first clear evidence in favour of starting insulinbased
treatment with basal insulin

19. Consistent achievement of glycaemic targets with basal insulin GLARGINE
HbA1c (%)
APOLLO3
LAPTOP4
Triple Therapy5
LANMET2
Treat-To-Target1
INITIATE6
7.14
7.15
6.96
6.80
8.71
8.85
8.80
9.5
8.61
Baseline
Study endpoint
58.0
Target HbA1c ≤7% (%)
49.4
48.0
57.0 NA 7 8 9 10 6
The most studied basal insulin
With established CV safety,
10 million patients,
> 60 million patient-years,
>59,000 participants in clinical trials
The efficacy of insulin glargine has been shown in numerous clinical studies:
Treat-to-Target: open-label, multicenter study (n=756), patients randomized to glargine (n=367) or NPH insulin (n=389) for 24 weeks.1
LANMET: open-label, multicenter study, in insulin-naïve T2D patients randomized to bedtime glargine plus metformin (n=61) or NPH insulin plus metformin (n=49) for 36 weeks.2
APOLLO: open-label study. T2D patients received OHAs plus once-daily glargine (n=174) or mealtime insulin lispro (n=174) for 44-weeks.3
LAPTOP: open-label study. Insulin-naïve patients with T2D (n=364) randomized to once-daily morning glargine plus OHAs (n=177) or twice-daily premixed human 70/30 insulin (n=187) for 24 weeks.4
Triple therapy: open-label trial, in T2D patients receiving OHAs (n=217). Randomized to additional once-daily insulin glargine at bedtime (n=105) or oral rosiglitazone (n=112) for 24 weeks.5
INITIATE: 58 patients with T2D given bedtime insulin glargine for 24 weeks as part of a group education program.6
In each study, glargine reduce baseline HbA1c levels to 7%, or close to this target.
1. Riddle M, et al. Diabetes Care 2003; 26: ; 2. Yki-Järvinen H, et al. Diabetologia 2006; 49: ; 3. Bretzel RG, et al. Lancet 2008; 371: ; 4. Janka H, et al. Diabetes Care 2005; 28: 254-9; 5. Rosenstock J, et al. Diabetes Care 2006; 29: 554-9; 6. Yki-Jarvinen H, et al. Diabetes 2006; 55 Suppl. 1: A30
1Riddle M, et al. Diabetes Care 2003;26:3080–6; 2Yki-Järvinen H, et al. Diabetologia 2006;49:442–51; 3Bretzel RG, et al. Lancet 2008;371:1073–84; 4Janka H, et al. Diabetes Care 2005;28:254–9; 5Rosenstock J, et al. Diabetes Care 2006;29:554–9; 6Yki-Jarvinen H, et al. Diabetes 2006;55 Suppl. 1:A30 19

20. Insulin Profiles: Premixed 30/70 Aspart
400
Isoglycemic clamp study
risk
HYPO
HYPER
HYPER
HYPER
300
risk
HYPO
pre-mixes
are NOT suitable to
Treat-to-target A1C <7.0%
Plasma Insulin (pM)
200
100 4 8 12 16 20
24 hrs
Inadequate prandial insulin : Postprandial Hyperglycemia
Excess inter-prandial supply: Increased risk of Hypoglycemia
Luzio S et al, Diabetologia 49:1163-8, 2006

21. 2015 – Basal & “Premix” Premix :
Fixed ratio.2
Premix :
Less flexible.1
Less studied alternative.1
Less adaptable.2
Less desirable to intensify.3
More Hypos & weight gain
Unable to titrate individually
“The fixed-ratio nature of premixed formulations make them less flexible & adaptable to the individual’s specific needs than a basal-plus strategy”.2
1. Diab Care 38; 38:140–149 Jan Owens DR. Diabet. Med. 30, 276–288; AACE Algorithm 2013

22. CLINICAL EVIDENCES for basal/basal-plus/basal-bolus strategy versus premixed

23. LAPTOP study: Comparison of insulin glargine added to an OAD regimen versus switching to premixed insulin
RANDOMISATION
Insulin glargine + OADs (n = 177) Initial dose: 10 IU once daily in the morning
Patients with T2DM HbA1c: 7.5% to 10.5% and FBG: ≥6.7 mmol/L (≥120 mg/dL) and treated with OADs (n = 364)
Human premixed insulin (70/30) (n = 187)
Initial dose: 10 IU before breakfast and 10 IU before dinner
Screening
Run-in phase
Treatment phase
3–14 weeks
24 weeks
Subjects taking sulphonylurea and metformin for at least a month were enrolled. Sulphonylurea was replaced with 3 or 4 mg glimepiride during run-in phase. OHA dose remained the same throughout the study in the insulin glargine arm, while OHAs were discontinued in the premixed insulin arm.
Janka H, et al. Diabetes Care 2005;28:254–9.

24. Significantly greater reduction in FBG and PPBG with insulin glargine vs premix16
Premixed insulin twice daily
Insulin glargine + OHAs 14
Baseline 12
Blood glucose (mmol/L) 10 * 8 * * 6 * *
Endpoint 4
Fasting
After breakfast
Lunch
After lunch
Dinner
After dinner
Bedtime
03.00
*p < 0.05 for treatment comparison of changes from baseline to endpoint
Time of day
Janka H, et al. Diabetes Care 2005;28:254–9.

25. HbA1c change from baseline (%)
Insulin glargine provided better glycaemic control and less weight gain than premix
Premixed insulin†
Insulin glargine‡
Final daily dose:
Premixed insulin 64.5 IU
Insulin glargine IU
-0.5
-1.0
-1.5
-2.0
2.5
2.0
1.5
1.0
0.5
2.1
p = NS
1.4
HbA1c change from baseline (%)
Weight gain (kg)
The LAPTOP trial randomised 371 patients whose T2DM was poorly managed with OHAs to receive once-daily insulin glargine plus OHAs or twice-daily premixed human insulin 30/70 without OHAs for 24 weeks.
The mean final HbA1c values were 7.2% and 7.5% in the insulin glargine and premixed insulin groups, respectively. More patients achieved the HbA1c target of ≤7% in the insulin glargine group (49% vs 39%; p=ns), and significantly more patients achieved this target without an episode of confirmed nocturnal hypoglycaemia in the insulin glargine group (46% vs 29%; p=0.0013).
The final mean FBG level was lower in patients receiving insulin glargine than in those receiving premixed insulin (6.4 mmol/l vs 7.4 mmol/l), and a greater proportion of patients achieved the FBG target of ≤5.6 mmol/l in the insulin glargine group (32% vs 15%; p=0.0001). Overall, the adjusted mean improvement in FBG level was greater in the insulin glargine group (p<0.0001).
Overall, the incidence of hypoglycaemia in the insulin glargine group was less than half that in the premixed insulin group (p<0.0001).
Patients reported weight gain in both groups: 1.4 kg and 2.1 kg, respectively (p=ns).
At the end of the trial, the mean daily insulin doses were 28 IU and 65 IU in the insulin glargine and premixed insulin groups, respectively.
In conclusion, insulin glargine had better efficacy and safety profiles than premixed human insulin when an intensive treat-to-target approach was followed.
Trial limitations: The trial compared a once-daily basal insulin plus OHAs with an a twice-daily basal and prandial insulin mixture without OHAs.
Janka H, et al. Diabetes Care 2005;28:254−9.
-1.31
-1.64
p =
Premixed insulin†
Insulin glargine‡
†Twice daily; ‡plus OHAs
Janka H, et al. Diabetes Care 2005;28:254–9.

26. Lower incidence of hypoglycaemia with insulin glargine versus premixed12
Premixed insulin
Insulin glargine*
9.87 10 8
p =
Events per patient per year
5.73 6
4.07 4
2,62
p = 2
1,04
0.51
All confirmed
hypoglycaemia
Confirmed symptomatic
Confirmed nocturnal
Hypoglycaemia confirmed by blood glucose <60 mg/dL (3.3 mmol/L)
*Plus ODAs
Janka H, et al. Diabetes Care 2005;28:254–9.

27. INITIATE (Raskin) study: Comparative study of insulin glargine versus premix added to an OAD regimen
RANDOMISATION
Insulin glargine + OADs (n = 114): Initiated at 10–12 U once daily at bedtime
Insulin-naïve patients with T2DM previously treated with metformin (>1,000 mg/day) alone or plus other OADs HbA1c ≥8% (n = 222)
Premixed insulin aspart (BIAsp 70/30) + OADs (n = 108)
Initiated at 5–6 U twice daily, before breakfast and dinner
[The American INITIATE trial included insulin-naïve patients with T2DM who where receiving suboptimal treatment with metformin alone or with other OHAs. Metformin doses were maximised and other OHAs discontinued before patients were randomised to receive once-daily insulin glargine or twice-daily premixed insulin aspart 30/70 for 28 weeks.]
A subpopulation (n=157) from INITIATE who did not use thiazolidinediones was considered separately in
The mean final HbA1c values were 7.4% and 6.9% in the insulin glargine and premixed insulin groups, respectively. Fewer patients achieved the HbA1c target of <7.0% in the insulin glargine group than in the premixed insulin group (41% vs 65%; p=0.003).
Mean FBG levels were reduced to similar levels but remained above target (≤6.1 mmol/l) in both groups.
Hypoglycaemia was less frequent in the insulin glargine group (p<0.0013).
Weight gain was significantly lower in the insulin glargine group (p=0.0004).
Insulin doses were titrated in a treat-to-target manner. The mean total insulin dose was initially the same in the two groups, but rose to 0.6 IU/kg and 0.9 IU/kg in the insulin glargine and premixed insulin groups, respectively.
In summary, while premixed insulin aspart 30/70 appeared more efficacious that insulin glargine, it was associated with an increased risk of hypoglycaemia and weight gain.1
Trial limitations: The trial compared a once-daily basal insulin with a twice-daily basal and prandial insulin mixture.2 The high FBG target and above-target final FBG level suggest that this agent was not optimally titrated. Secretagogues were discontinued in patients receiving insulin glargine, thereby removing postprandial cover in these patients.2
1. Raskin P, et al. Eur J Intern Med 2007;18:56–62.
2. Halbron M, et al. Diabetes Metab 2007;33:316–20.
Screening
Run-in phase
Treatment phase
3–14 weeks
28 weeks
During run-in, metformin was optimised to 1,500–2,550 mg/day, secretagogues and -glucosidase inhibitors were discontinued. Pioglitazone was continued (if taken pre-study) and subjects taking rosiglitazone were changed to pioglitazone.
Raskin P, et al. Diabetes Care 2005;28:260–5.

28. HbA1c was reduced in both groups with a significantly greater effect with premixed
Target FPG* achieved by 57% of insulin glargine group and 36% of premix group
HbA1c<7% achieved by 40% of insulin glargine group and 66% of premix group 16 12
Premix
14,0
13,5 14
Insulin glargine
9,7
9,8 10
p < 0.01 12 8
7,4 10
6,9
(%)
p = NS
FPG (mmol/L) 8
7,1 1c 6
6,5
The American INITIATE trial included insulin-naïve patients with T2DM who where receiving suboptimal treatment with metformin alone or with other OHAs. Metformin doses were maximised and other OHAs discontinued before patients were randomised to receive once-daily insulin glargine or twice-daily premixed insulin aspart 30/70 for 28 weeks.
Final mean HbA1c values were 7.4% and 6.9% in the insulin glargine and premixed insulin groups, respectively (p<0.01). Fewer patients in the insulin glargine group achieved an HbA1c <7.0% than in the premixed insulin group (40% vs 66%; p<0.001).1
Mean FBG levels were similarly reduced but remained above target (≤6.1 mmol/l) in both groups. More patients in the insulin glargine group achieved the FBG target (57% vs 36%).1
Insulin glargine was associated with a lower incidence of hypoglycaemia (p<0.05).1
Weight gain was also lower in the insulin glargine group (p<0.01).1
Insulin doses were titrated in a treat-to-target manner. Although similar at the start of the trial, daily insulin doses were 51.3 IU of insulin glargine and 78.5 IU of premixed insulin at trial end (p<0.05).1
Overall, premixed insulin aspart 30/70 appeared more effective than insulin glargine, but was associated with an increased risk of hypoglycaemia and weight gain.1
Trial limitations: The trial compared a once-daily basal insulin with a twice-daily basal and prandial insulin mixture.2 The high FBG target and above-target final FBG level, as well as the relatively low final dose of insulin glargine, suggest that this agent was not optimally titrated. Secretagogues were discontinued in patients receiving insulin glargine, thereby removing postprandial cover in these patients.2
1. Raskin P, et al. Diabetes Care 2005;28:260–5.
2. Halbron M, et al. Diabetes Metab 2007;33:316–20.
HbA 6 4 4 2 2
Baseline
Study end
Baseline
Study end
*FPG target of 80–110 mg/dL (4.4–6.1 mmol/L)
Raskin P, et al. Diabetes Care 2005;28:260–5.

29. Hypoglycaemia, weight gain and daily dose all lower with insulin glargine vs premix
Daily insulin dose 50
100 6 43
5,4
p < 0.05
p < 0.01
p < 0.05
78,5 40 5 80 4 30
3,5 60
51,3
% patients
IU at study end kg 3 20 16 40 2 10 20 1
Premixed
Insulin
Premixed
Insulin
Premixed
Insulin
insulin
glargine
insulin
glargine
insulin
glargine
*Minor hypoglycaemia: <56 mg/dL (<3.1 mmol/L) with or without symptoms
Raskin P, et al. Diabetes Care 2005;28:260–5.

30. GINGER: Basal Bolus provides superior glycemic control vs
GINGER: Basal Bolus provides superior glycemic control vs. intensified premixed insulin therapy
Subjects:
310 with inadequately controlled type 2 diabetes (HbA1c 8–11%)
Pretreated with premixed insulin (mean of 5 years), with some receiving metformin (continued during study)
Mean baseline values:
HbA1c (%): 8.5
BMI (kg/m2): 30.1
Diabetes duration (years): 13.0
Insulin glargine + three daily doses of insulin glulisine +/- metformin (n=153)
GINGER aimed to demonstrate that Basal Bolus provides superior glycemic control compared with premixed insulin in subjects with poorly controlled T2D.
This open-label, multinational study included 310 subjects with HbA1c of 7.5–11% who had previously been receiving premixed insulin.
Participants randomly received either Basal Bolus therapy with once-daily glargine plus three daily doses of mealtime glulisine (± OHAs, n=153), or optimized twice-daily premixed insulin (± OHAs, n=157), for 52 weeks.
In each study arm, insulin was titrated to preprandial BG target of 100 mg/dL (5.6 mmol/l) and a postprandial BG of 135 mg/dL (7.5 mmol/l).
N.B. all subjects were receiving premixed insulin before the study. Subjects randomly allocated to premix treatment did not simply continue their existing regimen, their treatment was optimized, i.e. the doses and treatment were adjusted.
Fritsche A, et al. Diabetologia 2008;51 Suppl. 1:S83
Randomization
Twice-daily premixed insulin +/- metformin (n=157)
52 weeks
Fritsche A, et al. Diabetologia 2008;51 Suppl. 1:S83

31. GINGER: Basal Bolus provides superior glycemic control vs
GINGER: Basal Bolus provides superior glycemic control vs. intensified premixed insulin therapy
p=0.0004
% achieving HbA1c <7.0 10 20 30 40 50
Glargine + glulisine
Premixed insulin 47 28
Months
7.0
8.0
9.0
6.0
p=0.0001 3 6 9 12
8.5
8.6
7.7
7.3
HbA1c (%)
Premixed insulin
Glargine + glulisine
Basal Bolus has superior efficacy to premixed insulin, including in T2D subjects inadequately controlled on premixed insulin.
Glargine starting dose was ~50% of patients’ total daily insulin at baseline (recommended minimum 16 U). Titration was based on 2-day mean FBG:
2 day mean FPG Dose adjustment
≤100 mg/dl No change
>100 mg/dl and ≤120 mg/dl Increase 2 U/daily
>120 mg/dl and ≤140 mg/dl Increase by 4 U/daily
>140 mg/dl and ≤160 mg/dl Increase by 6 U/daily
>160 mg/dl Increase by 8 U/daily
Glulisine starting dose was ~50 % of total daily baseline insulin (recommended minimum 3 x 6 U) titrated to achieve a 2-day post-prandial BG (PPBG) of ≤135 mg/dl:
2 day mean PPBG Dosage adjustment
≤135 mg/dl No change
>135 – ≥160 mg/dl Increase by 1 U daily
>160 – ≥200 mg/dl Increase by 2 U daily
>200 mg/dl Increase by 3 U daily
Premixed insulin was titrated to achieve preprandial BG≤ 100 mg/dl and postprandial BG ≤ 135 mg/dl according to mean 2-day pre-breakfast and pre-dinner BG values
2 day mean pre-meal BG Dosage adjustment
≤100 mg/dl No change
>100 – ≥120 mg/dl Increase by 2 U daily
>120 – ≥140 mg/dl Increase by 4 U daily
>140 – ≥160 mg/dl Increase by 6 U daily
>160 mg/dl Increase by 8 U daily
At study end, Basal Bolus delivered significantly lower HbA1c than premixed insulin (7.3% vs. 7.7%; p=0.0001), and more Basal Bolus patients achieved HbA1c <7% (47% vs. 28%; p=0.0004). Fritsche A, et al. Diabetologia 2008;51 Suppl. 1:S83
Fritsche A, et al. Diabetologia 2008;51 Suppl. 1:S83

32. GINGER: Basal Bolus has an acceptable safety profile in late stage T2D1 2 3 4
Glargine + glulisine
Premixed insulin
Mean body weight change from baseline (kg)
3.6
2.2
p=0.007
Symptomatic hypo
(event/patient-year) 5 10 15
Glargine + glulisine
Premixed insulin
9.9
13.4
p=NS
Severe hypo (event/patient-year)
0.00
0.05
0.10
0.15
0.20
0.25
Glargine + glulisine
Premixed insulin
0.1
0.2
p=NS
The rates of symptomatic hypoglycemia were 9.9 and 13.4 events/patient-year in the Basal Bolus and premixed insulin groups, respectively.
The rates of severe hypoglycemia were 0.1 and 0.2 events/patient-year in the glargine plus glulisine and premixed insulin groups, respectively.
Thus, Basal Bolus dose not increase the incidence of hypoglycemia compared with premixed insulin.
Basal Bolus recipients gained more weight than those receiving premixed insulin (3.6kg vs. 2.2kg; p=0.007).
The mean daily insulin dose at study end was 98.0 U in the glargine plus glulisine group and 91.3 U in the premix group (p=0.003). Baseline insulin doses were approximately 53 in the glargine plus glulisine group and 59 U in the premix group
Fritsche A, et al. Diabetologia 2008;51 Suppl. 1:S83
Fritsche A, et al. Diabetologia 2008;51 Suppl. 1:S83

33. Treatment satisfaction with insulin glargine vs premixed insulin analogues

34. LADI – switching from premixed to glargine + glulisine improves treatment satisfaction in T2DM
DTSQ score
[A 12-week observational study investigated the effectiveness of switching from premixed insulin therapy to a regimen of once-daily insulin glargine with insulin glulisine 1–3 times daily. Patients were previously receiving premixed human insulin (91%) or premixed insulin analogues (9%).
Patients with T2DM (n=1,674) and T1DM (n=123) were included in the study, which reported significant reductions in HbA1c values (p<0.0001). Hypoglycaemia was not well recorded. Weight was stable during the study.]
Diabetes Treatment Satisfaction Questionnaire scores (maximum score 36) for the T2DM population are shown here. The mean score improved from 18 at baseline to 29 at the end of the study (p<0.0001).
Study limitation: This was a short observational study and not a clinical trial. However, the study does provide real-life data to support clinical trial findings.
Schreiber S, et al. Diabetologia 2007;50(suppl 1):S410–1.
Baseline 12 weeks
Basal-plus and basal-bolus insulin therapy provided better patient treatment satisfaction
Schreiber S, et al. Diabetologia 2007;50(suppl 1):S410–1.

35. Treatment satisfaction is higher with insulin glargine than with premixed human insulin15
14.0
p =
11.5 10
DTSQc score at endpoint 5
This 24-week trial enrolled 364 patients whose T2DM was poorly controlled with OHAs. Patients received once-daily insulin glargine with OHAs or twice-daily premixed human insulin 30/70 without OHAs.1
Insulin doses were titrated using a weekly forced-titration schedule to reach a FBG target of ≤5.6 mmol/l.
The mean decrease in HbA1c was greater in the insulin glargine group (1.6% vs 1.3%; p=0.0003), and more patients achieved the HbA1c target of ≤7.0% without nocturnal hypoglycaemia (46% vs 29%; p=0.0013).1
A Diabetes Treatment Satisfaction Questionnaire, change version (DTSQc), was completed by 253 patients. Scores were similar at baseline, but were significantly higher in the insulin glargine group than in the premixed insulin group at trial end (14.0 vs 11.5; maximum score 18; p=0.0012).1
In conclusion, insulin glargine therapy was associated with a greater improvement in treatment satisfaction than premixed human insulin.
In contrast to premixed insulins, insulin glargine does not need to be taken at fixed mealtimes or require strict carbohydrate counting. Such dietary restrictions can affect a patient’s quality of life, and therefore impact on treatment satisfaction.2
1. Bradley C, et al. Diabetes 2005;54(Suppl):Abstract 1246-P.
2. Bradley C, et al. Diabetes Obes Metab 2008;10(Suppl 2):50–65.
Insulin glargine + OADs
Premixed human insulin 30/70 BID
At 24 weeks insulin glargine was associated with a greater increase in patient treatment satisfaction
Bradley C, et al. Diabetes 2005;54(Suppl):Abstract 1246-P.

36. High physician satisfaction with switching from premixed insulin to insulin glargine
Very good
Good
Satisfactory
Unsatisfactory
No response given
Efficacy
Safety
46%
42%
54%
41%
[This 12-week, open-label, non-interventional, cross-over trial was conducted in Germany. Patients with T2DM (n=6,308) receiving various premixed insulin therapies switched to once-daily insulin glargine treatment. Concomitant OHA use was at the patients’ physicians‘ discretion.
Switching from premixed insulin therapy to once-daily insulin glargine with OHAs significantly improved glycaemic control with a low risk of hypoglycaemia.]
Physicians were asked to document their experiences of treating patients with insulin glargine (4 point-scale: ‘very good’ to ‘unsatisfactory’).
Insulin glargine therapy was rated ‘good’ or ‘very good’ for glycaemic control (87%) and safety profile (96%). Insulin glargine was also rated ‘good’ or ‘very good’ for quality of life (94%), weight management (69%) and demand on physician's time (90%).
At the end of the trial, 98% of patients planned to continue insulin glargine therapy.
Trial limitations: Physician experiences were not recorded for premixed insulin therapy before switching; no comparison of treatment satisfaction is therefore possible.
Hammer H and Klinge A. Int J Clin Pract 2007;61:2009–18.
Most physicians rated the efficacy and safety of insulin glargine as ‘very good’ or ‘good’
Hammer H and Klinge A. Int J Clin Pract 2007;61:2009–18.

37. Markers of glycemic variability were better in patients treated with BB than in those treated with MIX in better control group.
Conclusion: These results suggest that BB therapy achieves better glucose profiles than MIX therapy.

38. Subcontinental Data

39. Addition of insulin aspart with basal insulin is associated with improved glycemic control in Indian patients with uncontrolled type 2 diabetes mellitus
Banerjee S, Maji D, Baruah M. J Assoc Physicians India Jan;61(1 Suppl):24-7.

40. Recent 2015 ADA Standard of care
Basal insulin alone is the most convenient initial insulin regimen, beginning at 10 U or 0.1–0.2 U/kg, depending on the degree of hyperglycemia.
Basal insulin is usually prescribed in conjunction with metformin and possibly one additional noninsulin agent.
A less studied alternative, transitioning from basal insulin to twice-daily premixed (or biphasic) insulin analog (70/30 aspart mix, 75/25 or 50/50 lispro mix), could also be considered.
Regular human insulin and human NPH-Regular premixed formulations (70/30) are less costly alternatives to rapid-acting insulin analogs and premixed insulin analogs, respectively, but their pharmacodynamic profiles make them suboptimal for the coverage of postprandial glucose excursions.
ADA STANDARDS OF MEDICAL CARE IN DIABETES—2015

41. Conclusion Basal Insulin strategy:
Simple, flexible approach to intensifying a basal insulin regimen.
Easily progressed to a basal-bolus regimen, if required.
Premixed insulin regimens are less flexible & must be switched to a more physiological basal-bolus regimen if further intensification is required.
Switching from premixed insulin regimens to basal ± boluses improves patient satisfaction.
The basal-bolus regimen offers patients flexible treatment that responds to different needs and lifestyles and reduces glucose variability

42. Thank you Initiate Study2 Laptop Study1 Hammer & Kingler3
AT-LANTUS Study5
Thank you
DURABLE Study5
Janka H, et al. Diabetes Care 2005;28:254–9.
2. Raskin P, et al. Diabetes Care 2005;28:260–5.
3. Davies M, et al. Diabetes Res Clin Pract 2008;79:368–75.
4. Hammer H and Klinge A. Int J Clin Pract 2007;61:2009–18
5. Diabetes Care 34:249–255, 2011.