Table 3.

Treatment trials with rhIGF-I in patients with severe INSR-related insulin resistance syndromes (SIR).

Author	Treatment Duration of rhIGF-I	SIR Syndrome (n)	Dosage	Efficacy and Safety
Quin et al., 1990 [23]	Short term 1 dose	RMS (1 patient)	100 μg/kg/day i.v.	Blood glucose, plasma insulin, C-Peptide and growth hormone (GH) declined
Schoenle et al., 1991 [24]	Short term 2 doses	Type A IR (3 patients)	100 μg/kg/day i.v.	Blood glucose, plasma insulin and C-peptide decreased
Hussain et al., 1993 [22]	Short term 4 days, BID	Type A IR (1 patient)	160 μg/kg/day s.c.	Lowering of fasting and postprandial blood glucose, insulin and C-peptide levels
Kuzuya et al., 1993 [73]	Up to 16 months	Type A IR (6 patients) DS (2 patients) Congenital lipodystrophy (2 patients) Other (1 patient)	100 to 400 μg/kg/day	Lowering of fasting and postprandial glucose. Decrease of HbA1c and fructosamine
Morrow et al., 1994 [27]	3–4 weeks	Type A without insulin receptor mutations (2 patients)	100 μg s.c.	Reduction of blood glucose level, enhancement of insulin sensitivity
Backeljauw, 1994 [75]	66 h and 62 h	DS (2 patients)	Up to 110 μg/kg/h and 40 μg/kg/h i.v.	No apparent glucose lowering effect, decrease in insulin concentration
Zenobi, 1994 [25]	5 days	Type A IR (2 patients)	150 μg/kg 2x/day s.c.	Decrease of fasting blood glucose. Decrease in fasting insulin and C-peptide by 65%
Longo et al., 1994 [63]	16 months	RMS (1 patient)	Up to 100 μg/kg/day s.c.	No significant effect on glycaemic control and growth
Nakashima et al., 1995 [28]	9 months	Type A IR (1 patient)	0.08–0.2 mg/kg/day s.c.	Decrease in blood glucose level, free fatty acid concentration, HbA1c; enhanced insulin sensitivity, improvement of acanthosis nigricans
Vestergaard et al., 1997 [26]	2 weeks high dose rhIGF-I	SIR (4 patients)	60 μg/kg 2x/day s.c.	Reduction of fasting blood glucose and insulin
	10 weeks low dose rhIGF-I	SIR (3 patients)	40 μg/kg/day s.c.
Takahashi et al., 1997 [32]	6 months	Leprechaunism—1 patient	100 μg/kg/day up to 1000 μg/kg/day	Fasting blood glucose, insulin, HbA1c, body weight and development improved
Nakae et al., 1998 [29]	6 years and 10 months	DS (?) or RMS (?) (1 patient at different time points)	Up to 1.6 mg/kg/day	Maintained growth rate, HbA1c near normal range
Kitamei et al., 2004 [78]			Intermittent and continuous s.c injection	Adult height was 143 cm (−2.7 SDS for Japanese girls)
Jo et al., 2013 [77]	Withdrawl of rhIGF-I treatment at 18 years, due to diabetic ketoacidosis and start of high dose insulin			Recurrent episodes of ketoacidosis. HbA1c up to 12–13%
Regan et al., 2010 [79]	16 weeks	Type A IR (5 patients)	0.5–2 mg/kg rhIGF-I/rhIGFBP-3	HbA1c improvement, reduction of acanthosis nigricans
Weber et al., 2014 [30]	16 months (from 19 months up to 35 months—death of the patient)	DS (1 patient)	BID 80 up to 640 μg/kg/day s.c.; At 30 months: continuous s.c. infusion via insulin pump: 800–1200 μg/kg/day	HbA1c improvement from 9.5 to 7.7%, rebound to 9.8% Improvement of HbA1c from 9.8 to 8.8%, Moderate weight gain
De Kerdanet et al., 2015 [48]	8.7 years; 2 years	DS (1 patient)	IGF-I/IGFBP3 combination, subsequ. IGF-I alone 50 μg/kg/day s.c.	Decrease in mean glycaemia with large variation. Improvement of growth.
Carmody et al., 2016 [31]	5 years	RMS (1 patient)	rhIGF-I up to 1.72 U/kg 2x/day s.c. + metformin	Decrease in insulin, homa index and HbA1c. Growth maintained within target height range.