Obesity in Patients with Type 1 Diabetes: Links, Risks and Management Challenges

Figures & data

Figure 1 In patients with type 1 diabetes adipose tissue deposits produce adipokines and inflammatory cytokines that induce insulin-resistance contributing to the development of cardiometabolic complications. The coexistence of these clinical characteristics of type 2 diabetes in patients with type 1 diabetes has been referred to as double diabetes.

Figure 2 Illustration of the main modifiable and endogenous biological factors implicated in obesity etiology.

Table 1 Anti-Obesity Pharmacological Therapy in Randomised Clinical Trials (>1 Year of Duration), Including Subjects with Type 2 Diabetes

	Duration (Years)	Participants (n)	Weight Loss		≥5% Weight Loss		Dropouts	Side Effects	Contraindications
			Drug	Placebo	Drug	Placebo
Orlistat ^Citation92								Oily spotting, flatus with discharge, diarrhea, fecal urgency	Chronic malabsorption syndrome, cholestasis and oxalate nephrolithiasis
Meta-analysis	1–4	6196	−6.4%	−3.5%	54%	33%	≈ 30%
Naltrexone-Bupropion								Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea	Uncontrolled hypertension, seizures, eating disorders, chronic opioid use, concurrent use with monoamine oxidase inhibitors within 14 days
COR-1^Citation93	1	1742	−6.1%	−1.3%	48.0%	16.0%	50%
COR-2^Citation94	1	1496	−6.4%	−1.2%	50.5%	17.1%	46%
COR-BMOD^Citation95	1	793	−9.3%	−5.1%	66.4%	42.5%	48%
COR-DIABETES^Citation96	1	505	−5.0%	−1.8%	44.1%	26.3%	48%
Phentermine/topiramate								Paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth	Glaucoma, hyperthyroidism, concurrent use with monoamine oxidase inhibitors within 14 days
CONQUER ^Citation97	1	2487
4(7.5/46 mg)		498	−7.8%	−1.2%	62%	21%	30.9%
(15/92 mg)		995	-9.8%	-1.2%	70%	21%	36.0%
SEQUEL ^Citation99	2	676
(7.5/46 mg)		227	-9.3%	-1.8%	75.2%	30%	17.6%
(15/92 mg)		295	-10.5%	-1.8%	79.3%	30%	16.9%
EQUIP ^Citation98
(15/92 mg)
OB-202/DM-230 Study^Citation100	1	1026	10.9%	-1.6%	66.7%	17.3%	41.2%
Plus CONQUER	1	451	-9.6%	-2.6%	65%	24%	19.7%
Liraglutide 3.0 mg (SCALE studies) ^Citation101								Nausea, vomiting, constipation or diarrhea	Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
Obesity/prediabetes ^Citation102	1	3731	−8.0%	−2.0%	63.2%	27.1%	18%
	3	2254	-6.1%	-1.9%	49.6%	23.7%	47.4%
Maintenance diabetes ^Citation104	1	422	-6.2%	-0.2%	50.5%	21.2%	25%
	1	846	-6.0%	-2.0%	69.2%	27.2%	26.7%

Notes: Subjects with diabetes were included in specific clinical trials (COR-DIABETES, SCALE Diabetes). For phentermine-topiramate, sub-studies were used that included patients with T2D, such as OB-202/DM-230 and a sample from the CONQUER study.

Abbreviations: COR, Contrave Obesity Research; BMOD, behaviour modification; SCALE, Satiety and Clinical Adiposity — Liraglutide Evidence.

Table 2 Studies Analysing the Effects of Oral Glucose-Lowering Drugs as Adjuncts to Insulin Treatment in T1D

			n	Duration (Weeks)	Change in HbA1c (%)	Change in Weight (kg)	Change in Insulin Dose
Biguanides
REMOVAL^Citation113		Metformin 1000 mg	428	156	−0.13**	−1.17**	−0.05 IU/kg/d
GLP1a
Lira-1^Citation120	Liraglutide 1.8 mg		100	24	−0.2	−6.80*	−0.1 IU/kg/d
ADJUNCT ONE^Citation121	Liraglutide 1.8 mg		1398	52	−0.2 **	−4.90 **	−5%* (∆BL)
	Liraglutide 1.2 mg				−0.15*	−3.55**	−2% (∆BL)
	Liraglutide 0.6 mg				−0.09*	−2.19**	+4% (∆BL)
ADJUNCT TWO^Citation122	Liraglutide 1.8 mg		853	26	−0.35 **	−5.10**	Ratio 0.90**
	Liraglutide 1.2 mg				−0.23**	−4.00**	Ratio 0.93**
	Liraglutide 0.6 mg				−0.24**	−2.50**	Ratio 0.95**
iSGLT2
DEPICT-1^Citation124	Dapagliflozin 10 mg		833	52	−0.36** (∆BL)	−3.90**	NR
	Dapagliflozin 5 mg				−0.33** (∆BL)	−2.56**	NR
DEPICT-2^Citation125	Dapagliflozin 10 mg		815	24	−0.42**	−3.74%^†	−16.71%
	Dapagliflozin 5 mg				−0.37**	−3.21%^†	−11.19%
EASE-1^Citation126	Empagliflozin 25 mg		75	4	−0.53*	−1.90**	−0.07 IU/kg/d*
	Empagliflozin 10 mg				−0.38**	−1.80**	−0.09 IU/kg/d *
	Empagliflozin 2.5 mg				−0.49**	−1.50**	−0.08 IU/kg/d *
EASE-2^Citation127	Empagliflozin 25 mg		730	52	−0.45***	−3.60***	−12.9%***
	Empagliflozin 10 mg				−0.39***	−3.20***	−12.0%***
EASE-3^Citation127	Empagliflozin 25 mg		977	26	−0.52***	−3.40***	−12.6%***
	Empagliflozin 10 mg				−0.45***	−3.00***	−9.5%***
	Empagliflozin 2.5 mg				−0.28***	−1.80***	−6.4%***
InTandem1^Citation128	Sotagliflozin 400 mg		793	52	−0.31**	−4.34**	−12.64%**
	Sotagliflozin 200 mg				−0.25**	−3.14**	−8.02**
InTandem1^Citation129	Sotagliflozin 400 mg		782	52	−0.32%*	−2.18**	−8.17%**
	Sotagliflozin 200 mg				−0.21%*	−1.98**	−6.26%*
InTandem1^Citation130	Sotagliflozin 400 mg		1402	24	−0.46**	−2.98**	−5.3 UI/d **
Amylin mimetics
Whitehouse et al^Citation133	Pramlintide 30µg or 60µg		480	52	−0.39**	NR	+2.3%* (∆BL)
Edelman et al^Citation134	Pramlintide 30µg or 60µg		296	29	−0.19	−1.3***(∆BL)	−12% (∆BL)
Ratner et al^Citation135	Pramlintide 60µg or 90µg		651	52	−0.29**	NR	NR

Notes: ^†Mean percent change. *p<0.05. **p<0.001. ***p<0.0001.

Abbreviations: ∆BL, change from baseline; NR, not reported.

Table 3 Studies Analyzing the Effects of Bariatric Surgery in Patients with T1D

Study	n	Type of Surgery	Follow-Up	Mean Decrease in BMI	Mean Reduction in Insulin UI/kg	Mean Changes in HbA1c (%)	Improvement in CVRF
Czupryniak et al^Citation144 2010	3	RYGB (n=3)	6.3 years	8.7	0.23	↓3	BP, dyslipidemia
Mendez et al^Citation145 2010	3	RYGB (n=3)	1year	16.5	0.20	↑0.07
Garcia-Caballero et al 2013^Citation157	5	SAGB (n=5)	19m	7	47 UI/d	↓1.6	BP, dyslipidemia
Raab et al 2013^Citation148	6	RYGB (n= 2); SG (n=1) BPD (n=3)	1 year	13.8	0.57	↓1.2
Chuang et al 2013^Citation147	2	RYGB (n=1); SG (n=1)	20m	18.1	↑0.05	↑1.95	BP, dyslipidemia
Fuertes-Zamorano et al 2013^Citation146	2	SADI-S (n=2)	4.5 years	23.0	0.26	↓0.85	Dyslipidemia
Reyes Garcia et al, 2013^Citation158	1	RYGB (n=1)	10 m	14.6	88UI	↓1.3
Blanco et al 2014^Citation142	7	RYGB (n=7)	2 years	12.1	↑0.01	↓0.1 NS	–
Brethauer et al 2014^Citation150	10	RYGB (n=7); SG (n=1), GB (n=2)	3years	11.1	0.34	↓1.1	BP, dyslipidemia
Tang et al 2014^Citation151	6	RYGB (n=1), SG (n=2), GB (n=3)	16 m	11.4	NR	↑0.1 NS	–
Lanno et al 2014^Citation152	22	RYGB (n=16); SG (n=6)	37 m	8.7	0.3	↓0.2 NS	–
Middelbeek et al 2015^Citation153	10	RYGB (10)	5years	9.7	0.05	↑1.7	Increase in HDL
Maraka et al 2015^Citation154	10	RYGB (n=9), SG (n=1)	2 years	13.1	NR	↓0.4 NS	Dyslipidemia
Robert et al 2015^Citation155	10	BPD (n=7), SG (n=3)	4.5years	16.5	0.7	↓0.4 NS	BP, dyslipidemia
Rottenstreich et al 2015^Citation160	13	RYGB (n=) SG (n=10)	2years	9.8	0.19	↓0.8 NS	BP
Vilarrasa et al 2017^Citation163	32	RYGB (n=11); SG (n=15), DS (n=6)	4.6 years	9.0	0.3	↑0.2NS	BP, dyslipidemia, OSA
Faucher et al 2016^Citation161	13	RYGB (n=6); SG (7)	1year	11.5	0.33	↓0.7
Moreno-Fdez et al 2016^Citation159	6	RYGB (n=3), SG (n=3)	4.5 years	14.2	0.10	↓0.6 NS	Triglycerides
Al Sabah et al 2017^Citation162	10	SG (n=10)	4 years	10.5	0.46	↓0.3 NS
Landau et al 2019^Citation156	26	RYGB (n=10); SG (n=5); GB (n=8)	3.5 years	9.3	NR	↑0.04 NS	BP, increase HDL
Hoskuldsdóttir et al 2020^Citation170	387	RYGB (n=387)	9 years	12	NR	↓0.8	CV disease and CV mortality

Abbreviations: BP, blood pressure; OSA, obstructive sleep apnea; CV, cardiovascular; RYGB, Roux- en-Y gastric bypass; SAGB, single anastomosis gastric bypass; SG, sleeve gastrectomy; GB, gastric banding; SADI-S, single anastomosis duodeno-ileal bypass with sleeve gastrectomy; DS, duodenal switch.

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