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Introduction A post hoc analysis of the PIONEER 1–5 and 8 trials assessed the clinically relevant composite endpoints of HbA1c (glycated haemoglobin) reduction ≥ 1% and body weight loss of ≥ 5% or ≥ 10% with orally administered semaglutide versus comparators. Methods In the PIONEER trials, people with type 2 diabetes were randomised to orally administered semaglutide versus placebo (PIONEER 1, 4, 5 and 8), empagliflozin (PIONEER 2), sitagliptin (PIONEER 3) and liraglutide (PIONEER 4) for 26–78 weeks. This analysis assessed the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% at week 26 and at end of treatment, and the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment. Results Overall, 3506 people in PIONEER 1–5 and 8 were included. At week 26 and at end of treatment, odds of achieving the composite endpoint of an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% were significantly greater with orally administered semaglutide 14 mg than with placebo (PIONEER 1, 4, 5 and 8; all p

Aim\ud \ud Treat‐to‐target, randomized controlled trials have confirmed lower rates of hypoglycaemia at equivalent glycaemic control with insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 1 (T1D) or type 2 diabetes (T2D). Treat‐to‐target trials are designed to enable comparisons of safety and tolerability at a similar HbA1c level. In this post hoc analysis of the SWITCH 1 and 2 trials, we utilised a patient‐level modelling approach to compare how glycaemic control might differ between basal insulins at a similar rate of hypoglycaemia.\ud \ud \ud \ud Materials and Methods\ud \ud Data for HbA1c and symptomatic hypoglycaemia from the SWITCH 1 and SWITCH 2 trials were analyzed separately for patients with type 1 diabetes and type 2 diabetes, respectively. The association between the individual patient‐level risk of hypoglycaemia and HbA1c was investigated using a Poisson regression model and used to estimate potential differences in glycaemic control with degludec versus glargine U100, at the same rate of hypoglycaemia.\ud \ud \ud \ud Results\ud \ud Improvements in glycaemic control increased the incidence of hypoglycaemia with both basal insulins across diabetes types. Our analysis suggests that patients could achieve a mean HbA1c reduction of 0.70 [0.05; 2.20]95% CI (for type 1 diabetes) or 0.96 [0.39; 1.99]95% CI (for type 2 diabetes) percentage points (8 [1; 24]95% CI or 10 [4; 22]95% CI mmol/mol, respectively) further with degludec than with glargine U100 before incurring an equivalent risk of hypoglycaemia.\ud \ud \ud \ud Conclusion\ud \ud Our findings suggest that patients in clinical practice may be able to achieve lower glycaemia targets with degludec versus glargine U100, before incurring an equivalent risk of hypoglycaemia.

This report presents the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) as initial injectable therapy at 26 weeks in the 104‐week DUAL VIII durability trial (NCT02501161). Participants (N = 1012) with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs) were randomized 1:1 to open‐label IDegLira or IGlar U100. Visits were scheduled at weeks 1, 2, 4 and 12, and every 3 months thereafter. After 26 weeks, glycated haemoglobin (HbA1c) reductions were greater with IDegLira versus IGlar U100 (−21.5 vs. –16.4 mmol/mol [−2.0 vs. –1.5%]), as was the percentage of participants achieving HbA1c

Aims Evaluate 26 weeks’ liraglutide treatment in type 1 diabetes (T1D) by subgroups in the ADJUNCT ONE and TWO trials. Materials and Methods ADJUNCT ONE and TWO were randomized controlled phase 3 trials in 1,398 and 835 participants with T1D treated with liraglutide (1.8, 1.2 or 0.6 mg) or placebo (adjuncts to insulin). This post hoc analysis evaluated treatment effects by subgroups: HbA1c (textless or ≥ 8.5; body mass index (BMI) (textless or ≥ 27 kg/m2) and insulin regimen (basal bolus or continuous subcutaneous insulin infusion). Results In both trials at week 26, reductions in HbA1c, body weight and daily insulin dose did not differ significantly (ptextgreater0.05) by baseline HbA1c or BMI. Risk of clinically significant hypoglycemia or hyperglycemia with ketosis did not differ significantly (ptextgreater0.05) by baseline HbA1c, BMI or insulin regimen. At week 26 in ADJUNCT ONE, these risks did not differ (ptextgreater0.05) between treatment groups. Placebo-adjusted reductions in HbA1c, body weight and insulin dose (-0.30 points, -5.0 kg, and -12 respectively, with liraglutide 1.8 mg) were significant (ptextless0.05), greater than at week 52 and similar to those in ADJUNCT TWO (-0.35 -4.8 kg and -10 respectively, with liraglutide 1.8 mg). Conclusions In ADJUNCT ONE and TWO, the efficacy and glycemic safety of liraglutide did not depend on subgroups, leaving residual beta-cell function the only identified parameter impacting the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in T1D. These findings support a role for GLP-1 RAs as adjuncts to insulin in T1D, warranting further study. Abstract Aim To evaluate 26 weeks of liraglutide treatment in type 1 diabetes (T1D) by subgroups in the ADJUNCT ONE and ADJUNCT TWO trials. Materials and Methods ADJUNCT ONE and ADJUNCT TWO were randomized controlled phase 3 trials in 1398 and 835 participants with T1D treated with liraglutide (1.8, 1.2, or 0.6 mg) or placebo (adjuncts to insulin). This post hoc analysis evaluated treatment effects by subgroups: HbA1c (< or ≥8.5%), body mass index (BMI; < or ≥27 kg/m2), and insulin regimen (basal bolus or continuous subcutaneous insulin infusion). Results In both trials at week 26, reductions in HbA1c, body weight, and daily insulin dose did not differ significantly (P > .05) by baseline HbA1c or BMI. Risk of clinically significant hypoglycaemia or hyperglycaemia with ketosis did not differ significantly (P > .05) by baseline HbA1c, BMI, or insulin regimen. At week 26 in ADJUNCT ONE, these risks did not differ (P > .05) between treatment groups. Placebo-adjusted reductions in HbA1c, body weight, and insulin dose (−0.30%-points, −5.0 kg, and −12%, respectively, with liraglutide 1.8 mg), were significant (P

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce body weight (BW). Evidence suggests that GLP-1RAs directly modulate appetite and reduce food intake through central mechanisms. However, GLP-1RAs are also associated with gastrointestinal (GI) adverse events (AEs), which may contribute to reduced appetite and food intake. We sought to assess whether the BW loss observed in phase 3 clinical trials with oral semaglutide was primarily due to indirect effects (defined as GI AEs, specifically nausea, vomiting, and diarrhea) or direct effects (not explained by GI AEs). Data from PIONEER 1-5, 7, and 8 were assessed and a mediation analysis (how a third variable [GI AEs] affects the relationship between two other variables [treatment and BW]) was performed to separate the overall contribution of direct and indirect effects to changes in BW. Significant total estimated treatment differences in BW loss were observed vs. all comparators with oral semaglutide 7 mg (1.0-3.7 kg vs. placebo, 1.7 kg vs. active comparator) and 14 mg (2.7-5.0 kg vs. placebo, 0.8-2.4 kg vs. active comparators). In the mediation analysis, GI AEs accounted for 0.0-0.3 kg of the BW loss across oral semaglutide doses vs. all comparators (Figure). In conclusion, GI AEs (indirect effects) appear to have no clinically relevant impact on total BW loss observed with oral semaglutide vs. placebo and most active comparators. Disclosure J. J. Meier: Advisory Panel; Self; AstraZeneca, MSD Corporation, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, MSD Corporation, Novo Nordisk, Sanofi. R. Agesen: Employee; Self; Novo Nordisk. L. Bardtrum: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. A. Y. Cheng: Advisory Panel; Self; Abbott, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Research Support; Self; Applied Therapeutics, The Medicine Company, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bausch Health, Canada, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi. S. Deenadayalan: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. E. Montanya: Advisory Panel; Self; Sanofi, Consultant; Self; Merck Sharp & Dohme Corp., Employee; Spouse/Partner; Almirall, S. A., Research Support; Self; Menarini Group, Roche Diagnostics SL, Speaker’s Bureau; Self; Novo Nordisk A/S. R. E. Pratley: Other Relationship; Self; Hanmi Pharmaceutical, Merck Sharp & Dohme Corp., Metavention, Monster Energy Company, Inc., Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. Funding Novo Nordisk A/S

We re-evaluated the efficacy and safety of liraglutide, a GLP-1 analog, for use as adjunctive therapy in people with type 1 diabetes (T1D). Results from the two ADJUNCT trials suggested that residual beta-cell function is associated with more pronounced benefits and less risk of hypoglycemia. Here we analyze results of the two trials according to other baseline anthropometrics. ADJUNCT ONE (NCT01836523) and TWO (NCT02098395) were randomized controlled phase 3 trials in broad T1D populations (1398 and 835 participants, respectively) treated with liraglutide (1.8, 1.2 or 0.6 mg) or placebo. ADJUNCT ONE was a 52-week trial with a treat-to-target design and no limits on insulin titration; ADJUNCT TWO was a 26-week trial with an individual maximal insulin dose. In a post hoc analysis, we evaluated certain estimated placebo-adjusted treatment effects across clinically relevant participant subgroups. At week 26 in ADJUNCT ONE, placebo-adjusted reductions in HbA1c, body weight (BW) and daily insulin dose (up to -0.30 %-points, -5.0 kg and -12%, respectively, with liraglutide 1.8 mg) were significant (p0.05) on baseline HbA1c or BMI at neither week 26 nor 52. The risk of clinically significant hypoglycemia (symptomatic episodes with blood glucose 0.05 vs. placebo) by baseline HbA1c, BMI or insulin regimen. In ADJUNCT ONE and TWO, the efficacy and glycemic safety of liraglutide did not depend on key baseline anthropometrics. This leaves residual beta-cell function the only identified parameter impacting the treatment effect of the GLP-1 analog used as an adjunct to insulin in T1D. Together with recent progress in the understanding of T1D and of the benefits of GLP-1 receptor agonism, these findings suggest a role for GLP-1 receptor agonists in T1D, warranting further study. Disclosure T. F. Dejgaard: Advisory Panel; Self; Novo Nordisk, Consultant; Self; Boehringer Ingelheim International GmbH, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. L. Bardtrum: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. E. Christiansen: None. F. Kreiner: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. S. Madsbad: Advisory Panel; Self; AstraZeneca; Boehringer Ingelheim; Eli Lilly; Merck Sharp & Dohme; Novo Nordisk; Sanofi, Research Support; Self; Novo Nordisk, Boehringer Ingelheim, Speaker’s Bureau; Self; AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi. M. G. Von herrath: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. B. Von scholten: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. C. Mathieu: Advisory Panel; Self; Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma, Research Support; Self; Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics, Speaker’s Bureau; Self; Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca and Novartis. Funding Novo Nordisk A/S

AIMS To investigate whether the proven benefits of insulin degludec (IDeg) combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes. MATERIALS AND METHODS This was a post hoc pooled analysis of 5 phase III randomized, 26-week, open-label, treat-to-target trials comparing IDegAsp twice daily (n = 1111) with one of two comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) categories, as well as by baseline duration of diabetes or body mass index (BMI) categories. RESULTS We conducted a meta-analysis of 5 clinical trials: NCT01513590, NCT01009580, NCT01059812, NCT01680341 and NCT01713530. End-of-trial results were broadly consistent, with differences between IDegAsp and comparators observed in phase III trials. HbA1c results were similar for IDegAsp and the comparators in all baseline characteristic (HbA1c, duration of diabetes or BMI) and category groups (number ranges). Significantly lower FPG level was observed with IDegAsp vs comparators in all baseline characteristic and most category groups (excluding FPG

Introduction DUAL II Japan (NCT02911948) was a 26-week, phase 3a randomized, treat-to-target trial which compared the efficacy and safety of IDegLira with degludec in 210 Japanese patients with type 2 diabetes (T2D) uncontrolled on premixed or basal insulin therapy. The DUAL II Japan trial presented the opportunity for a post hoc analysis to examine the safety and efficacy of switching patients from a premixed regimen (containing both basal and bolus insulin components) to IDegLira. Methods Patients from DUAL II Japan were stratified according to prior insulin regimen (premixed or basal insulin). The following endpoints were assessed in this post hoc analysis by pre-trial insulin regimen: change in HbA1c, body weight, daily total insulin dose, nine-point self-measured blood glucose, and severe or blood glucose-confirmed hypoglycemia (defined as severe or plasma glucose less than 56 mg/dL). Results This post hoc analysis included 39 patients who switched from premixed insulin to IDegLira. The treatment effect in this population was independent of insulin type at baseline (premixed or basal; interaction test, P = 0.2535). In patients switching from premixed insulin to IDegLira, mean [standard deviation (SD)] HbA1c was 8.26% (0.73) at baseline and 6.68% (0.93) at week 26. Mean (SD) body weight was reduced by 1.5 (2.9) kg. At week 26, daily insulin dose was 34.2 dose steps. After 26 weeks, the mean prandial increment was smaller at all meals with IDegLira irrespective of pre-trial insulin regimen. Rate of hypoglycemic events was 2.59 events/patient-year of exposure over the 26 weeks. Conclusion This post hoc study is the first to evaluate the switch from premixed insulin to IDegLira in patients with uncontrolled T2D. IDegLira initiation resulted in improved HbA1c and weight loss. This study offers insight into the effectiveness and safety of switching patients from premixed insulin therapy to IDegLira, and provides support for further investigation. Trial Registration NCT02911948. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-00730-y) contains supplementary material, which is available to authorized users.

Aims/Introduction Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). The present study investigated the pharmacodynamic properties of IDegAsp in Japanese patients with type 1 diabetes mellitus. Materials and Methods In this randomized, double-blind, two-period, cross-over trial, 21 Japanese patients with type 1 diabetes mellitus received single doses of 0.5 U/kg IDegAsp and biphasic insulin aspart 30 in a randomized sequence (13–21 days washout between treatments). The pharmacodynamic response was evaluated in a 26-h euglycemic glucose clamp (target 5.5 mmol/L). Single-dose IDegAsp glucose infusion rate (GIR) profiles were extrapolated to steady state using modeling. Results The IDegAsp single-dose GIR profile showed a clear distinction between the effects of the bolus (IAsp) and basal (IDeg) components in IDegAsp. When simulated to steady state, the GIR profile of IDegAsp was shifted upwards compared with the single-dose profile, and showed a rapid onset of action and a distinct peak from the IAsp component followed by a separate and sustained basal action from the long-acting IDeg component. For biphasic insulin aspart 30, the initial shape of the GIR profile was similar to IDegAsp, but GIR continuously decreased from maximum and reached zero 18–20 h post-dosing. The characteristics of the GIR profile for IDegAsp were retained when simulated to steady state in a twice-daily dosing regimen. Discussion In Japanese patients with type 1 diabetes mellitus, the pharmacodynamic profile of IDegAsp is characterized by distinct prandial and basal effects from the IAsp and IDeg components, consistent with what has been reported previously in Caucasian patients with type 1 diabetes mellitus.

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of long-acting insulin degludec and short-acting insulin aspart. This open-label, Phase 1 study aimed to determine the pharmacodynamic and pharmacokinetic properties of IDegAsp in children (6-11 yr), adolescents (12-17 yr), and adults (18-65 yr) with type 1 diabetes mellitus (T1DM). Thirty-eight subjects received single subcutaneous IDegAsp dosing (0.5 U/kg) immediately before a standardized liquid meal (17.3 g carbohydrates/100 mL; adjusted for body weight) followed by plasma glucose (PG) and pharmacokinetic blood sampling for 36 and 57 h, respectively. There were no apparent differences between age groups in PG lowering effect (AUCPG baseline,0-6 h,meal,SD ), maximum PG excursion (ΔPGmax,meal,SD ), or maximum PG concentration (PGmax,meal,SD ) after the standardized meal. Estimated ratios (ERs) for total exposure (AUCIAsp,0-12 h,SD ) and maximum concentration (Cmax,IAsp,SD ) of IAsp in IDegAsp were children/adults, 1.69 (95% confidence interval, CI: 1.02; 2.80) and 1.66 (95% CI: 1.10; 2.51); adolescents/adults, 1.14 (95% CI: 0.76; 1.69) and 1.16 (95% CI: 0.84; 1.61). ERs for total exposure (AUCIDeg,0-∞,SD ) and maximum concentration (Cmax,IDeg,SD ) of IDeg in IDegAsp were children/adults, 1.42 (95% CI: 0.94; 2.16) and 1.38 (95% CI: 1.09; 1.76); adolescents/adults, 1.23 (95% CI: 0.96; 1.58) and 1.16 (95% CI: 0.95; 1.42). IDegAsp was well tolerated across age groups. The fast onset of prandial coverage of IAsp in IDegAsp and the ultra-long pharmacokinetic properties of IDeg in IDegAsp were preserved in children and adolescents. Exposure to IAsp and IDeg seemed to be higher in children vs. adults, but no differences were observed in PG lowering effect. IDegAsp could be an alternative treatment option in children and adolescents with T1DM.

Background Historically, data on the rate of hyperglycemia and ketosis have not been collected in clinical trials. However, it is clinically important to assess the rate of these events in children with type 1 diabetes (T1D). This question was addressed in two pediatric trials using insulin degludec (degludec). Objective To assess the rate of hyperglycemia and ketosis in two-phase 3b trials investigating degludec (Study 1) and degludec with insulin aspart (IDegAsp [Study 2]) vs insulin detemir (IDet). Subjects Patients (aged 1-17 years inclusive) with T1D treated with insulin for ≥3 months. Methods Study 1: patients were randomized to degludec once daily (OD) or IDet OD/twice daily (BID) for 26 weeks, followed by a 26-week extension phase. Study 2: patients were randomized to IDegAsp OD or IDet OD/BID for 16 weeks. Bolus mealtime IAsp was included in both studies. In Study 1, hyperglycemia was recorded if plasma glucose (PG) was >11.1 mmol/L, with ketone measurement required with significant hyperglycemia (>14.0 mmol/L). In Study 2, hyperglycemia was recorded with PG >14.0 mmol/L where the subject looked/felt ill, with ketone measurement also required in these hyperglycemic patients. In this post hoc analysis, the hyperglycemia threshold was 14.0 mmol/L for uniformity. Results Despite similar rates of hyperglycemia with degludec/IDegAsp compared with IDet, the rates of ketosis were lower with degludec/IDegAsp. Conclusions These trials, the first to systematically collect data on ketosis in pediatric patients with T1D, demonstrate the potential of degludec/IDegAsp to reduce rates of metabolic decompensation, compared with IDet.

Introduction The present study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg) in Japanese patients with type 1 diabetes. Materials and Methods This was a randomized, single‐center, double‐blind, two‐period, crossover, multiple‐dose trial. Patients were randomized into two treatment sequences, and received IDeg or insulin detemir for 6 days and a washout period (7–21 days) before switching treatment. Blood samples for pharmacokinetic measurements were obtained before each dose and up to 120 h after the last dose of each treatment period. Pharmacodynamic measurements were obtained using a 26‐h euglycemic clamp procedure after the last dose of each treatment period. Results A total of 22 patients were randomized (14 men, 8 women; mean glycosylated hemoglobin at baseline of 7.5% [based on Japanese Diabetes Society value]). At steady state, total glucose‐lowering effect (area under the glucose infusion rate [GIR] curve during one dosing interval [τ, 0–24 h] at steady state [AUCGIR ,τ, SS]) was 1,446 mg/kg and total exposure (geometric mean) of IDeg (AUCID eg,τ, SS) was 81,270 pmol h/L. Both the glucose‐lowering effect and the exposure of IDeg were evenly distributed over the dosing interval, with AUC for the first 12‐h intervals being approximately 50% of the total (geometric mean; AUCGIR ,0–12h, SS/AUCGIR ,τ, SS = 48%; AUCID eg,0–12h, SS/AUCID eg,τ, SS = 53%). Conclusions IDeg has a flat, consistent and ultra‐long glucose‐lowering effect that is evenly distributed across a 24‐h interval and an ultra‐long duration of action in Japanese patients with type 1 diabetes. These data support once‐daily dosing of IDeg in all patients. Overall, the pharmacodynamic and pharmacokinetic end‐points and safety observations are consistent with those previously reported in Caucasian patients.

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of long-acting insulin degludec and short-acting insulin aspart. This open-label, Phase 1 study aimed to determine the pharmacodynamic and pharmacokinetic properties of IDegAsp in children (6-11 yr), adolescents (12-17 yr), and adults (18-65 yr) with type 1 diabetes mellitus (T1DM). Thirty-eight subjects received single subcutaneous IDegAsp dosing (0.5 U/kg) immediately before a standardized liquid meal (17.3 g carbohydrates/100 mL; adjusted for body weight) followed by plasma glucose (PG) and pharmacokinetic blood sampling for 36 and 57 h, respectively. There were no apparent differences between age groups in PG lowering effect (AUC

From 1992 tol999 more than 500 funnel experiments were car ried out with robins, redstarts, whitethroats, and pied flycatchers. The purpose was to elucidate the orientation of birds caged and tested for a prolonged time in an inverted magnetic field, i.e. a field where the vertical component was reversed (pointed up wards). Contrary to expectations, the results did not suggest that orientation was governed by a magnetic inclination compass; generally no differences were found between birds tested in the inverted field and those tested in the natural one. However, occa sional patterns of (bimodal) orientation at right angles appeared, probably elicited by the inverted field, and contradictions be tween stellar and magnetic information. Possibly, the significance and kind of magnetic orientation in passerine birds is less well understood than is normally supposed.