Comparing Efficacy and Safety of Thrice Daily Versus Twice Daily NovoMix® 30 (Biphasic Insulin Aspart 30) in Subjects With Type 2 Diabetes Inadequately Controlled With Basal Insulin

Percentage of subjects achieving HbA1c <7.0% (yes or no) was evaluated after 24 weeks of treatment.

Percentage of subjects achieving HbA1c <7.0% (yes or no) without severe hypoglycaemic episodes was evaluated after 24 weeks of treatment. Severe hypoglycaemia: Episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose (PG) concentrations may not be available during event, but neurological recovery following return of PG to normal is considered sufficient evidence that the event was induced by low PG concentration.

Percentage of subjects achieving HbA1c <7.0% (yes or no) without severe or BG confirmed hypoglycaemic episodes (according to the Novo Nordisk classification) was evaluated after 24 weeks of treatment. Severe or BG confirmed hypoglycaemia: an episode that is severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose (PG) value <3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA: Episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. PG concentrations may not be available during event, but neurological recovery following return of PG to normal is considered sufficient evidence that the event was induced by low PG concentration.

ADA classification of hypoglycaemia:

1. Severe:Episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. PG concentrations may not be available during event, but neurological recovery following return of PG to normal is considered sufficient evidence that the event was induced by low PG concentration
2. Asymptomatic:Episode not accompanied by typical symptoms of hypoglycaemia, but with a measured PG concentration ≤3.9 mmol/L
3. Documented symptomatic:Episode during which typical symptoms of hypoglycaemia are accompanied by a measured PG concentration ≤3.9 mmol/L
4. Pseudo:Episode during which person with diabetes reports any of the typical symptoms of hypoglycaemia with measured PG concentration >3.9 mmol/L but approaching that level
5. Probable symptomatic:Episode during which symptoms of hypoglycaemia are not accompanied by PG determination but that was presumably caused by a PG concentration ≤3.9 mmol/L

Treatment emergent hypoglycaemic episodes were defined as the hypoglycaemic episodes, which occurred on or after the first day of trial product administration (in week 0), and no later than 7 days after the last day on trial product.

Novo Nordisk (NN) classification of hypoglycaemia:

1. Severe hypoglycaemia: According to the ADA classification.
2. Blood glucose (BG) confirmed hypoglycaemia: an episode that is BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia.
3. Severe or BG confirmed hypoglycaemia: an episode that is severe according to the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia.

Change from baseline in fasting plasma glucose (FPG) by central laboratory analysis was evaluated after 24 weeks of treatment. Missing data was imputed using the LOCF method.

7-point self-measured plasma glucose (SMPG) profiles was evaluated after 24 weeks of treatment.

Subjects were instructed to perform the following SMPG measurements:

1. Before breakfast.
2. 120 minutes after the start of breakfast.
3. Before lunch.
4. 120 minutes after the start of lunch.
5. Before main evening meal.
6. 120 minutes after the start of main evening meal.
7. At bedtime. Missing data was imputed using the LOCF method.

Change from baseline in 2-hour postprandial glucose (PPG) at individual meal (breakfast, lunch and main evening meal) was evaluated after 24 weeks of treatment. Missing data was imputed using the LOCF method.

Change from baseline in PPG increment at individual meal (breakfast, lunch and main evening meal) was evaluated after 24 weeks of treatment. Missing data was imputed using the LOCF method.

Change from baseline in mean of 2-hour PPG at individual meal (breakfast, lunch and main evening meal) was evaluated after 24 weeks of treatment. Missing data was imputed using the LOCF method.

Change from baseline in mean of PPG increment at individual meal (breakfast, lunch and main evening meal) was evaluated after 24 weeks of treatment. Missing data was imputed using the LOCF method.

Change from baseline in mean of the 7-point SMPG profiles was evaluated after 24 weeks of treatment. Missing data was imputed using the LOCF method.

Fluctuation in the 7-point SMPG profile was evaluated after 24 weeks of treatment. Fluctuation in 7-point SMPG profile was the average absolute difference to the mean of the profile of the 7-point SMPG measurements accumulated over the profile. Missing data was imputed using the LOCF method.

Incidence of TEAEs was recorded during 24 weeks of treatment. A TEAE was defined as an event that has onset date (or increase in severity) on or after the first day of exposure to trial product (in week 0) and no later than 7 days after the last day on trial product.

Total daily insulin dose was the sum of doses given before breakfast and before main evening meal for the BID treatment group, and the sum of doses given before breakfast, before lunch and before main evening meal for the TID treatment group. Missing data was imputed using the LOCF method.

Change from baseline in body weight was evaluated after 24 weeks of treatment. Missing data was imputed using the LOCF method.

Change from baseline in patient-reported treatment satisfaction (as assessed by the DTSQs) was evaluated after 24 weeks of treatment. The DTSQs is a self-completion questionnaire used to investigate the subject's treatment satisfaction. The DTSQ contained 8 questions, which were scored on a scale from 0 to 6. Out of 8 questions, 6 were related to the overall treatment satisfaction and 2 were related to glycaemic control (hypoglycaemia and hyperglycaemia). Results for the 6 questions relating to overall treatment satisfaction are presented together whereas the 2 questions relating to blood glucose are presented separately. For the overall treatment satisfaction, a higher score (0-36) was related to a better perception of treatment satisfaction. For hypoglycaemia and hyperglycaemia, a lower score (0-6) was related to a better blood glucose control. Missing data was imputed using the LOCF method.